Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV 'real life' trial on the variability of response to opioids.

BACKGROUND: Guidelines tend to consider morphine and morphine-like opioids comparable and interchangeable in the treatment of chronic cancer pain, but individual responses can vary. This study compared the analgesic efficacy, changes of therapy and safety profile over time of four strong opioids given for cancer pain. PATIENT AND METHODS: In this four-arm multicenter, randomized, comparative, of superiority, phase IV trial, oncological patients with moderate to severe pain requiring WHO step III opioids were randomly assigned to receive oral morphine or oxycodone or transdermal fentanyl or buprenorphine for 28 days. At each visit, pain intensity, modifications of therapy and adverse drug reactions (ADRs) were recorded. The primary efficacy end point was the proportion of nonresponders, meaning patients with worse or unchanged average pain intensity (API) between the first and last visit, measured on a 0-10 numerical rating scale. (NCT01809106). RESULTS: Forty-four centers participated in the trial and recruited 520 patients. Worst pain intensity and API decreased over 4 weeks with no significant differences between drugs. Nonresponders ranged from 11.5% (morphine) to 14.4% (buprenorphine). Appreciable changes were made in the treatment schedules over time. Each group required increases in the daily dose, from 32.7% (morphine) to 121.2% (transdermal fentanyl). Patients requiring adjuvant analgesics ranged from 68.9% (morphine) to 81.6% (oxycodone), switches varied from 22.1% (morphine) to 12% (oxycodone), discontinuation of treatment from 27% ( morphine) to 14.5% (fentanyl). ADRs were similar except for effects on the nervous system, which significantly prevailed with morphine. CONCLUSION: The main findings were the similarity in pain control, response rates and main adverse reactions among opioids. Changes in therapy schedules were notable over time. A considerable proportion of patients were nonresponders or poor responders. CLINICAL TRIAL REGISTRATION: NCT01809106 (https://clinicaltrials.gov/ct2/show/NCT01809106?term=cerp&rank=2).

Treatment of an aneurysm of the celiac artery arising from a celiomesenteric trunk. Report of a case.

INTRODUCTION: Visceral artery aneurysms (VAA) are rare, frequently present as a life-threatening emergency and are often fatal. The celiacomesenteric trunk (CMT), a common origin of the celiac trunk (CT) and the superior mesenteric artery (SMA) from abdominal aorta, is quite rare. Aneurysms that involve this celiomesenteric anomaly are even rarer and in the last 32 years have been reported in only 20 cases in the literature. PRESENTATION OF CASE: We describe a case with 30mm aneurysm arising from a CMT. In general, an aneurysm that is 20mm or greater in size is considered to be significant enough to warrant treatment. Abdominal VAA sometimes can be treated with low-invasive procedures: our patient required open surgical repair with the celiac artery replanted on to the aorta. DISCUSSION: The clinical course was complicated only by an increase of hepatic cytolysis enzymes, and by a low output pancreatic fistula, treated conservatively. The patient was discharged on the fifteenth postoperative day. One month after discharge, imaging revealed a good patency of all reconstructed arteries. In the subsequent 36-month follow-up period, the patient reported no clinical episodes. CONCLUSION: Our finding of a very rare case of a celiomesenteric anomaly with a concurrent aneurysm is extremely rare (20 cases in word literature in the last 32 years). The feasibility of the endovascular approach for aneurysms originating from the common celiomesenteric trunk depends mainly on aneurysmal location, diameter and neck size. In case of specific unfit anatomy, a careful surgical treatment can ensure the best results.

The role of splenectomy in myelofibrosis with myeloid metaplasia.

AIM: In this paper we retrospectively analyzed prospectively-collected data on our myelofibrosis with myeloid metaplasia (MMM) patients who underwent splenectomy. The aim was to ascertain the hematological response and any resolution of symptoms existing prior to splenectomy; redefining timing and role of splenectomy in the treatment of MMM. METHODS: This prospective study considered 31 patients with MMM who underwent splenectomy for transfusion-dependent anemia, thrombocytopenia, abdominal swelling and pain. Postoperative work-up consisting in laboratory tests and clinical evaluation performing a quality of life (QoL) test based on EORTC QLQ-C30 questionnaire. Follow-up data were collected for one year after surgery. Statistical analysis used Student's t-test, the Mann-Whitney rank sum, Fisher's exact test, the Friedman test and the Wilcoxon test. RESULTS: Mortality was 3.2%. Respiratory symptomatic complications occurred in 35.4%. In all patients the need for blood transfusions was significantly reduced (P=0.005). An improvement in the painful symptoms was reported and a significant improve of postoperative quality of life was observed at one year after surgery. CONCLUSION: In our experience splenectomy is associated with limited perioperative mortality and morbidity. Acute complications are almost exclusively limited to respiratory tract. The removal of spleen seems can be recommended to increase the QoL and to palliate hematological disorders in patients no more responder to chemotherapy.

[Internal carotid artery aneurisms: two cases]. / Anévrismes de l'artère carotide interne extra-crânienne: à propos de 2 cas.

INTRODUCTION: Aneurysms of the extracranial portion of the internal carotid artery (ICA) are rare (accounting for only 0.1-2% of all surgical procedures affecting the ICA, 0.4-1% of all arterial aneurysms, and 4% of all aneurysms involving peripheral arteries), but they are nonetheless clinically significant because of the high related risk of cerebral thromboembolism. Given the rarity of these lesions, it seems worthwhile to report on two extracranial ICA aneurysms, one of atherosclerotic, the other of fibrodysplastic etiology that came under our observation. PATIENTS AND METHODS: Our experience concerns just two cases, treated at the Department of Surgical and Gastroenterological Sciences of the Policlinico G.B. Rossi in Verona, presenting with very different clinical and instrumental findings, and requiring a different surgical treatment. The former underwent resection of the aneurysm and end-to-end reconstruction; in the latter, we performed a carotid transposition with internalization of the external carotid artery. RESULTS: Neither patient suffered from any major or minor neurological complications during or after surgery, and the follow-up confirmed a normal extracranial carotid patency. CONCLUSIONS: Based on our, albeit limited experience and an analysis of the literature, we make a few points concerning the diagnostic approach (which differs from the case of stenosing carotid lesions), the indications and type of treatment for extracranial ICA aneurysms.

[Laparoscopic treatment of liver hydatid cyst: personal technique]. / Il trattamento chirurgico laparoscopico delle cisti idatidee epatiche: tecnica personale.

Treatment of liver hydatid cyst is still controversial. Besides medical treatment, interventional radiologic techniques and traditional surgery, recently the laparoscopic approach has been proposed. Laparoscopic treatment of liver hydatid cyst, however, has not been well defined so far and seems to be associated with a recurrence rate from 0 to 9%, in a 3-49 months follow-up. Disadvantages of the laparoscopic approach are difficult control of spillage, peritoneal dissemination of parasites and incomplete aspiration of high density fluid contents of the cyst. The authors have reviewed the literature and describe a personal technique to avoid this disadvantage and to reduce postoperative recurrence rate.

[Treatment of celiac trunk aneurysms: personal experience and review of the literature]. / Traitement des anévrismes du tronc coeliaque: expérience personnelle et revue de la littérature.

INTRODUCTION: Celiac trunk aneurysms represent 4% of all splanchnic artery aneurysms. These lesions are thus extremely rare but yet have a significant clinical importance. Mortality, mainly related to site characteristics, is a significant risk (14%) in the event of rupture. PATIENTS AND METHODS: We put forward our experience in both diagnosis and treatment in three patients, two women and one man (average age 55.3 years, range 35-74), presenting aneurysms involving the celiac trunk. The preoperative diagnosis was established successively with ultrasonography, CT scan and angiography. Two patients were treated via an open surgical approach while endovascular percutaneous treatment was performed for the third patient. RESULTS: Mortality was null at 13 days on average from admission for the surgical patients and 4 days for the patient treated endovascularly. Postoperative complications were modest: pulmonary thickening with pleural effusion for the two surgical patients (spontaneous resolution), while for the third patient treated with an endovascular method, the stent migrated to a splanchnic arterial branch, with no consequence for the spleen. The average follow-up was 19 months (range 14-24). Full exclusion of the aneurysm was maintained at four months for the aneurysm treated percutaneously. A patent celiac was also maintained for the patients treated surgically. CONCLUSIONS: Considering the largely unforeseeable outcome and the high risk of rupture, we suggest that all the patients presenting this type of aneurysmal lesion should be treated. This attitude is widely advocated in the literature. Moreover, we noted null mortality in our small series, with only one percutaneous "re-do" case; resolutive at last control. With the present improvement in stent technology, endovascular treatment should be preferred. Patients should be treated surgically only if a percutaneous procedure would be risky or technically unfeasible due to the size of the aneurysm or its anatomic features.

Managing anomalous splenic artery aneurysm: a review of the literature and report of two cases.

The splenic artery originates from the superior mesenteric artery in approximately 1% of cases, which may explain the extreme rarity of aneurysms involving this anomalous branch, with only five cases reported in the international literature to date. We report our experience of managing two patients with aneurysms involving splenic arteries arising from the superior mesenteric artery, one treated surgically and the other percutaneously. From a diagnostic point of view, the first approach is ultrasound, while computed tomographic (CT) scan and angiography enable a better definition of the lesion and of the anatomical anomaly; CT angiography is currently the method of choice for the preoperative workup. Finding these two anomalies in association is so rare that it is impossible to draw any final conclusions as to the best type of treatment. In the authors' experience, both surgery and percutaneous treatment can prove useful.

Treatment of six hepatic artery aneurysms.

Hepatic artery aneurysms are rare lesions but of significant clinical importance because rupture is associated with elevated mortality. Although diagnosis using CT scanning and, more importantly, angiography has been well defined, the therapeutic choices are less clear. We retrospectively selected patients from 1985 to 2000 who were treated with either traditional surgical or percutaneous techniques. In total we treated six patients, four males and two females. This represents 17.6% of 34 patients treated by us for splanchnic artery aneurysms. The treatment was surgical in two cases (33.3%) and percutaneous in four cases (66.6%). All lesions were successfully treated with exclusion/ablation of the aneurysm. Mortality was nil; in one of the surgical cases we reported a transient hepatic failure and in the endovascular group, one right pleural effusion, one small splenic infarction, and one pseudoaneurysm of the gastroduodenal artery. The first therapeutic strategy to be taken into consideration is always the percutaneous approach. However, surgery still has a role in those cases where the lesion cannot be repaired percutaneously. Based on our own experience (good results, no mortality, and few complications) and in accordance with the literature, it is clear that an aggressive approach is warranted in those patients.

Previous appendicitis may affect peritoneal overlap of the mesh in laparoscopic inguinal hernia repair.

Laparoscopic inguinal hernia repair is now increasingly performed in bilateral and recurrent groin hernias. The avoidance of direct exposure of the commonly used meshes to the abdominal viscera is considered essential to reduce the risk of bowel adhesions. We report a case of bilateral inguinal hernia repair in a patients who had had an appendectomy performed 8 years earlier for a perforated appendicitis. Probably as a result of previous inflammation, any attempt to dissect the preperitoneal layer in the right side resulted in peritoneal lacerations. Since the peritoneum could not be used to cover the mesh, we decided to position an expanded polytetrafluoroethylene (e-PTFE) mesh to avoid postoperative adhesions. The mesh was fixed with tacks to the symphysis pubis, Cooper's ligament, the ilio-pubic tract, and the transversalis fascia 2 cm above the hernia defect. This case suggests that in patient with previous appendicitis, a difficult preperitoneal dissection can be expected. In such cases, especially in young patients for whom future surgical operations cannot be excluded, any attempt to reduce adhesions is justified. At the present time, the use of e-PTFE meshes, which induce no tissue reaction, is a good option in this situation.

[Multiple primary malignant neoplasms. Report of a rare case with 5 metachronous tumors]. / Le neoplasie maligne primitive multiple. A proposito di un raro caso con cinque tumori metacroni.

The Authors report on a patient admitted several times for the occurrence of five multiple metachronous primary malignancies (laryngeal carcinoma, endometrial adenocarcinoma, rectal cancerous polyp, ampulla of Vater carcinoma and transverse colon cancer). All five carcinomas were independent primary cancers, and the lengthy time intervals between the onsets of the individual tumours supports their independent non-metastatic origin. Classification, pathogenesis, genetic and environmental interactions of multiple tumours are discussed. In the case reported, a family history of colon cancer was present, while no genetic marker abnormalities or chronic exposure to carcinogens were found. The case report shows that an aggressive, appropriate surgical approach together with thorough follow-up monitoring offers a chance of long-term survival for patients with metachronous malignant primary tumours.

[Surgical treatment of redundant colon after retrosternal esophagocolonoplasty for caustic esophageal stenosis]. / Il trattamento chirurgico della ridondanza colica dopo esofagocolonplastica retrosternale per stenosi esofagea da caustici.

The Authors report two cases of transposed colon redundancy occurring after surgical treatment in 37 patients with caustic oesophageal strictures by retrosternal oesophagoplasty. Surgical management was required because of persistent dysphagia and weight loss in both patients. The technique performed was a resection of the redundant loop with a termino-terminal colo-colonic anastomosis via a right thoracic approach.

[Pancreatic pseudocysts. Our experience with 21 cases treated surgically]. / Le pseudocisti del pancreas. La nostra esperienza su 21 casi trattati chirurgicamente.

Twenty-one consecutive patients with pancreatic pseudocyst have been reviewed. Nine cases have been treated with internal drainage, 9 with external drainage, while 3 patients have undergone distal pancreatectomy. No mortality was associated to the surgical treatment, while morbidity was of 9.5% due to pancreatic fistulas. Based on their own experience and literature review the Authors describe clinical, diagnostic and therapeutic features of the disease and point out the good results of cistojejunostomy with Roux-en-Y loop.

[Stenotic endometriosis of the sigmoid. Apropos a case]. / L'endometriosi stenosante del sigma. A proposito di un caso.

The authors report a rare case of stenotic sigmoid endometriosis which presented with constipation and dysmenorrhea in a 48-year-old woman without past gynecological history. There were no typical radiological and endoscopic findings and only pathological examination revealed endometriosis. The patient did well after sigmoid resection and bilateral salpingo-oophorectomy and has had no further complaints. The authors stress the rare location of the disease and review the literature about etiopathogenetic hypotheses and pathological features. The diagnostic value of clinical examination, barium enema and colonoscopy is low as endometriosis rarely involves the mucosa. This case led the authors to discuss about diagnostic difficulties, differential diagnosis and therapeutic options.

[Malignant schwannoma of the small intestine: a report of 2 cases]. / Lo schwannoma maligno dell'intestino tenue: descrizione di due casi.

The authors report two cases of small bowel malignant schwannoma. It is an extremely rare disease and it is often difficult to diagnose malignancy. Histologic differentiation from other stromal tumors may require electron microscopy, although the preparation of immunohistochemical reactions now allows to identify forms which were previously diagnosed in different terms to be precisely classified. Diagnosis is often late and no preoperative test enables a correct clinical diagnosis to be made. The primary treatment is surgical and the resection is the only real therapy. Radiotherapy and chemotherapy are ineffective. Close postoperative observation is recommended because of the tendency to recurrence and metastasis.

[Malignant stromal tumors of the duodenum. Report of a case]. / I tumori stromali maligni del duodeno. A proposito di un caso.

The Authors report a rare case of undifferentiated duodenal malignant stromal tumour in a 69-years-old man radically managed by pancreaticoduodenectomy and resection of a liver metastasis. Several preoperative tests were performed (barium meal, endoscopy, ultrasonography and CT scan) but failed to yield a differential diagnosis between a tumour of the pancreatic head and a retroperitoneal neoplasm. The diagnosis was only histological. The tumour was considered to be high-grade due to its large size, high mitotic index, and the presence of necrosis and liver metastasis. Thorough surveillance revealed several hepatic metastases 29 months after resection, and chemotherapy performed at this stage proved completely ineffective. The patient died 38 months after surgery.

[Clinical-diagnostic and therapeutic considerations in a rare case of mesenteric cyst]. / Considerazioni clinico-diagnostiche e terapeutiche su un raro caso di cisti mesenterica.

The authors report a rare case of mesenteric cyst in a 36 years old woman. These cysts have a pathogenesis that primarily may be ectopic lymphatic tissue and their most common site is in the small bowel mesentery, especially of the ileum. In the case reported the cyst was located in the right mesocolon. Mesenteric cysts can appear as chronic abdominal pain, a painless abdominal mass, or acute abdomen. Diagnostic aids include abdominal computed tomography and sonography, that usually make diagnosis of mesenteric cyst. Treatment of choice is enucleation; resection of the adjacent bowel may occasionally be necessary.

[Carotid lesions and vascular risk factors]. / Lesioni carotidee e fattori di rischio vascolare.

BACKGROUND AND AIMS: Recent studies have underlined a significant incidence of peripheral arterial occlusive disease (PAOD) of the lower limbs in the general population which is often wrongly diagnosed. The "classic" risk factors--like dyslipidemia--are not always present in significant percentages in patients suffering from PAOD of the lower limbs. The aim of this study was to evaluate the incidence of the most common vascular risk factors (smoking, hypertension, hyperglycemia, dyslipidemia) in patients suffering from stenosing lesions of the extracranial carotid axes, comparing the data with similar findings in lower limbs. Moreover, the authors evaluated the association between these risk factors, carotid atheromatous lesions and ischemic cardiomyopathy (CI). METHODS: A retrospective study was performed to evaluate the data from 1643 patients examined consecutively. A total of 636 (age > 40, carotid stenosis > 40%, presence of risk factors) were considered eligible. RESULTS: The results showed that, contrary to the findings in patients suffering from PAOD, diabetes was not among the most frequently associated risk factors, whereas a relatively large number of patients had a history of smoking, including both smokers and ex-smokers. CONCLUSIONS: The difference in the most frequent risk factors identified for PAOD and carotid lesions suggests different etiopathogenetic mechanisms for the two districts.

[Self-expanding stents for the palliation of esophageal and gastric cardia cancer]. / L'impiego delle protesi autoespansibili nel trattamento palliativo del carcinoma dell'esofago e del cardias.

Twenty-one endoscopic tube implantations were carried out in 24 patients with malignant stenosis of esophagus and gastric cardia using self-expanding metallic stents. The indications to endoscopic intubation were advanced stage of the tumor in 17 cases and risk factors which made resection inadvisable in 7 cases. In 3 patients it proved impossible to implant a stent endoscopically because the Authors were not able to pass the guide wire through the stenosis, while correct stent placement was achieved in 21 patients. Functional results were good in 18 patients, while 3 patients did not have any improvement of symptoms. Complications occurred in 9 patients (42.85%): 2 bleedings, 3 neoplastic obstructions, 1 food obstruction and 3 distal dislodgements of the prostheses were observed, but could readily be corrected. No death occurred. The median survival time was 151 days (range 25-545). This study suggests that endoscopic placement of metallic self-expanding stents is safe and has to be preferred to plastic stents for easier implantation and lower morbidity.

[Unidentified arteriopathy: an epidemiological study. The preliminary results]. / L'arteriopatia misconosciuta: studio epidemiologico. Risultati preliminari.

The importance of the social and medical impact of arteriosclerotic disease fully justifies a series of studies focused on improving knowledge of this pathology before symptoms become manifest, so as to orientate treatment increasingly towards prevention. The aim of this study-of which the authors now report the preliminary results-was to establish the incidence of unidentified lower limb arteriopathy in the general population and to evaluate the relations between this and the possible presence of risk factors. The authors therefore decided to evaluate patients attending outpatient General Surgery clinic for symptoms manifestly not related to lower limb vascular pathology (arterial or venous). Patients suffering from any arterial disease were likewise excluded from the study. The importance of performing a large-scale epidemiological study (sample size, stratification of population studied, vast geographic area, etc.) persuaded the authors to adopt a multi-centre structure. Twelve General Surgery departments at hospitals in the Veneto area were involved: each was required to evaluate an average of 150 patients, giving a total of 1950 subjects. The method of study chosen was the residual pressure index (RPI) measured using Doppler velocimetry. Patients were divided into two study groups: patients in Group A (with pathological RPI) were re-evaluated after correction for risk factors, integrated or not by medical treatment. Preliminary results relating to 46% of the total sample show that 26.7% of the subjects present pathological RPI. The evaluation of risk factors and the comparison of their presence in the two groups (A--pathological patients, B--non-pathological subjects) reveals significant differences regarding diabetes and hypertension.