LARGE CELL METASTATIC PANCREATIC NEUROENDOCRINE CARCINOMA TREATED WITH SOMATOSTATIN ANALOGUES - CASE REPORT AND LITERATURE REVIEW.

We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient's health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. CONCLUSION: This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

PROGNOSTIC FACTORS IN PATIENTS WITH SURGICAL RESECTION OF PANCREATIC NEUROENDOCRINE TUMOURS.

CONTEXT: Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. OBJECTIVE: The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. SUBJECTS AND METHODS: The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. RESULTS: Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. CONCLUSIONS: Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%.

A rare case of ileal metastasis from cervical cancer.

We present the case of a 70-year-old woman, with a history of radiation-treated and surgically- resected cervical cancer, who was admitted to our clinic for intermittent sub occlusive symptoms. CT scan revealed a liver nodule and intestinal obstruction. The patient underwent surgery for excision of suspected liver metastasis and resolution of intestinal obstruction.Intraoperatively an ileal tumour was found to be the cause of the obstruction. Anatomo-pathological findings were consistent with an ileal metastasis from the cervical cancer.The liver nodule was only an area of focal steatosis.

Rare cause of intestinal obstruction - submucous lipoma of the sigmoid colon.

The lipoma of the colon is a benign and rare tumor. Most lipomas are asymptomatic, their discovery being fortuitous. The diagnosis is ussualy easy by colonoscopy associated with biopsies. The abdominal CT scan also has its role in the diagnostic process and in the assesment of the tumoral extension.The treatment depends essentially on the clinical picture, on the size and location of the lipoma and involves endoscopic or surgical excision. We present the case of a 56 years old woman in which a random colonoscopic and than tomographic diagnosis of a sigmoidian lipoma was made 2 years ago when the patient presented with different symptoms, the submucosal lipoma being small sized at the time; the surgical treatment(sigmoidectomy including the tumor) was currently indicated by the sub-occlusive syndrome and haematochezia, due to the intraluminal proliferation of the tumor.

A rare case of metastatic squamous urachal carcinoma.

Squamous cell carcinoma is a very rare type of urachal malignancy, only a few cases being reported in the medical literature. We present the case of a 49-year-old male patient diagnosed with infected squamous cell urachal carcinoma with multiple pulmonary metastases, after complaints of lower abdominal pain, abdominal mass and fever, without respiratory symptoms. The abdominal ultrasonography and the CT scan revealed a tumoral mass in the lower abdomen in contact with the abdominal wall and the urinary bladder dome, displacing the small bowel. Pulmonary nodular lesions were described in the left lobe pyramid. The intraoperative diagnosis was necrotic urachal tumor with urinary bladder dome invasion and suspected pulmonary metastases, and tumor ablation with bladder dome resection and suture of the bladder were performed. The histopathological result was poorly differentiated squamous cell carcinoma (G3), with negative resection margins. The patient recovered well after surgery, but the prognosis is very poor due to the metastatic stage in which the tumor was diagnosed, no standard chemotherapy regimen for the treatment of metastatic urachal carcinoma being known as effective until now.

Outcome of liver transplantation for hepatocellular carcinoma -- a single center experience.

BACKGROUND & AIMS: Liver transplantation (LT) is a promising treatment for patients with liver cirrhosis associated with hepatocellular carcinoma (HCC). The aim of our study was to evaluate our experience regarding the clinical and pathological staging of HCC in patients who underwent LT, as well as recurrence free and overall survival. METHODS: From January 2006 to December 2011, 38 patients with diagnosis of HCC, underwent LT in our Center. Demographic, clinical, imaging and pathologic information were recorded. A Cox proportional hazards survival analysis was performed in order to identify significant predictors of tumor recurrence and patient's death after LT. RESULTS: Eighteen patients (47.4%) in our study group were within Milan criteria. The mean follow-up was 22 months and the recurrence rate of HCC after LT was 13.2%. The 1, 3- year recurrence free survival rates were 85%, 74.3% respectively. The 1 and 3-year overall survival rates were 83.5% and 63.6% respectively. No significant predictor for HCC recurrence was identified in our study group by survival analysis, taking into account 13 different variables. As independent predictors of patient'ss death after LT for HCC however, the presence of diabetes mellitus (p=0.001), presence of more than 3 HCC nodules (p=0.03) and tumor recurrence after LT (p=0.03) were identified by multivariate Cox proportional hazards survival analysis. CONCLUSION: In our cohort HCC recurrence rate after LT was 13.2%. Diabetes mellitus, presence of more than 3 HCC nodules and HCC recurrence were significant predictors of poor overall survival after LT.

Morphological and immunohistochemical criteria of tissue response to radiotherapy in rectal cancer.

AIM: Given the context that rectal tumours respond to a certain degree to radiotherapy, a necessity arises for estimating a tumour's capacity to react to radiation from the very moment of diagnostic biopsy. MATERIAL AND METHODS: We have histologically and immunohistochemically analysed tissues coming from 52 patients with rectal adenocarcinomas. RESULTS: Of the studied parameters, the ones presenting significant variation under radiotherapy in terms of statistics(p 0.05) were: colloid type (p=0.001), EGFR in the tumour(p=0.00045), EGFR in the normal epithelium (p=0.0017),VEGF in the tumour (p=0.0132) and VEGF in the tumour stroma (p=0.030). CONCLUSIONS: Our study follows the same trends as the medical literature we have consulted regarding the variation of EGFR and VEGF with radiotherapy, and the distinct note of our study relies in the observation that normal stroma in case of rectal tumors also reacts to radiotherapy, sometimes more aggressively than the tumor itself, especially in which concerns the nerve and muscle fibers.

Intrahepatic cholangiocarcinoma--a rare indication for liver transplantation. Case report and review of the literature.

BACKGROUND: While hepatocellular carcinoma is a common indication for liver transplantation, intrahepatic cholangiocarcinoma represents a controversial indication for this procedure, due to lower disease-free and overall survival rates achieved by liver transplantation in such patients. Hence, in the last years, few centers reported satisfactory survival rates after liver transplantation for cholangiocarcinoma, in highly selected groups of patients. Herein we present the clinicopathological characteristics, the pre- and postoperative management and the favorable outcome of a patient undergoing liver transplantation for an unresectable intrahepatic cholangiocarcinoma. We consider that reporting the patients with such favorable outcomes is useful, since collecting the data presented by different centers may contribute to identification of a selected group of patients with cholangiocarcinoma who may benefit from liver transplantation. CASE REPORT: A 62-year old female patient with a primary liver tumor developed on HBV liver cirrhosis, was admitted in our center for therapeutical management. Since preoperative work-up suggested that the tumor is an unresectable hepatocellular carcinoma (due to its location and underlying liver disease), we decided to perform liver transplantation. The pathological examination of the explanted liver revealed that the tumor was a stage I intrahepatic cholangiocarcinoma. The postoperative course was uneventful, and in present, 15 months after transplantation, the patient is alive, without recurrence. CONCLUSIONS: Liver transplantation may represent a valid therapeutical option in selected patients with intrahepatic cholangiocarcinoma. Patients with early stage intrahepatic cholangiocarcinomas unresectable due to the underlying liver cirrhosis seem to benefit mostly by liver transplantation. Further studies are needed to identify the favorable prognostic factors in order to select the most appropriate candidates for liver transplantation. The most suitable immunosuppressive and (radio)chemotherapic regimens should be identified in the future, in order to improve the disease-free and overall survival rates of the patients undergoing liver transplantation for intrahepatic cholangiocarcinoma.

[Intestinal intussusception due to ileal gastrointestinal stromal tumor--a case report]. / Invaginatie intestinala prin tumora gastrointestinala stromala ileala--prezentare de caz.

Intestinal occlusion due to intussusception produced by intestinal tumors is a very rare condition. Gastrointestinal stromal tumors are also rare digestive neopasias, with an impredictable malignant behavior, which are usually growing outside the intestinal wall, being rarely the initiators of an intestinal intussusception. We present the case of a 59 years old female, admitted in our hospital to elucidate the etiology of her iron deficient anaemia, which developed an intestinal occlusion at the intestinal preparation for colonoscopy. The abdominal CT scan performed in emergency conditions highlighted occlusive intestinal tumor complicated with intestinal intussusception. We performed an emergency laparotomy that revealed intestinal occlusion due to ileo-ileal intussusception produced by an ileal tumor. The surgical intervention consisted in segmental ileal enterectomy including the tumor with latero-lateral entero-enteral anastomosis. The patient recovered without complications. The histopathological and immunohisto-chemical examinations established the diagnose of gastro-intestinal stromal tumor with high risk malignant behavior, therefore the patient was guided in the oncological department for specific treatment and oncological surveillance.

Isolated splenic metastasis of endometrial adenocarcinoma--a case report.

The spleen in rarely the place for solid, non-haematological tumors, isolated splenic metastases from adenocarcinomas being extremely rare findings, regardless of the origin and the histological type of the primary tumor. We present the case of a female patient with isolated splenic metastasis diagnosed by abdominal computer tomography at only 20 months after curative surgery for endometrial adenocarcinoma, in which the final diagnosis has been established by histological and immunohistochemical examination of the splenectomy piece. The haematogenous dissemination of the endometrial cancer occurs most commonly in the lungs, liver or bones, the spleen being rarely affected. In the medical literature there are cited up to date only 12 cases of solitary splenic metastasis from endometrial adenocarcinoma. The particularity of the case presented by us is the early appearance of an isolated splenic metastasis, at less than two years after curative surgery (compared to an average of 4-5 years cited in the literature), from an endometrial cancer which was classified histologicaly in the group with low-risk for relapse (well differentiated endometrioid adenocarcinoma). In conclusion, although solitary splenic secondary determinations are very rare, the incidence of the reported cases in the medical literature is increasing, their late appearance (a few years after the primary tumor's resection) and the lack of symptoms until the tumor reaches appreciable size or it complicates with necrosis, justifies the periodic abdominal imaging examination, on long-term, for postoperative monitorisation after the initial curative surgery. Their treatment of choice is open, classical splenectomy that must be followed by chemotherapy in order to prevent the development of other possible micrometastases.

[Diagnosis and surgical management in gastrointestinal neuroendocrine tumors]. / Managementul diagnosticului si tratamentul chirurgical în tumorile neuroendocrine gastrointestinale.

Neuroendocrine tumors, known as carcinoid tumors constitute a heterogeneous group of neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause specific clinical syndromes. Assessment of specific or general tumors markers offers high sensitivity in establishing the diagnosis and they also have prognostic significance. Management strategies include curative surgery, whenever possible-that can be rarely achieved, palliative surgery, chemotherapy, radiologic therapy, such as radiofrequency ablation and chemoembolisations and somatostatin analogues therapy in order to control the symptoms. The aim of this paper is to review recent publications in this field and to give recommendations that take into account current advances in order to facilitate improvement in management and outcome.

Prognostic and predictive potential molecular biomarkers in colon cancer.

An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

[An experimental model of transgastric ooforectomy using a porcine model]. / Stabilirea modelului experimental de ooforectomie transgastrica pe model suin.

INTRODUCTION: Transabdominal routes for surgery entail general anaesthesia with its inherent risks and complications (prolonged hospital stay, abdominal incisions that may be difficult in obese patients). Minimally invasive procedures require shorter hospitalization, have shorter recovery periods, less postoperative discomfort, and lower morbidity and complications. The purpose of this study was to use a porcine model to determine the feasibility and the safety of organ resection (oophorectomy and tubectomy). MATERIALS AND METHODS: 10 Big White pigs between 25-30 kg underwent transgastric ooforectomy. The first 5 cases were performed in a hybrid procedure (laparoscopic-NOTES) in order to have a better control and supervise the maneuvers done by the mobile endoscope and to guide in the abdominal cavity. RESULTS: Adnexectomy was possible in all ten experiments. Full operative time (from starting endoscopy to complete gastrectomy closing) was 180 min to 270 min. The gastric defect closing was the most difficult manoever lasting from 10 min with OTSC clips to 100 using endoloops and clips. The animals have tolerated well the experiments and there have been no remarkable incidents during our 10 experments. In only one case a bleeding from gastotomy required electric coagulation. CONCLUSION: Transgastric ooforectomy in an experimental model is a procedure that requires advanced laparoscopical and endoscopical skills. Our early results are promissing. Its application in humans needs further confirmation of the method.

[Liver transplantation--indications, surgical technique, results--the analysis of a clinical series of 200 cases]. / Transplantul hepatic--indicati, tehnica, rezultate-analiza unei serii clinice de 200 de cazuri.

INTRODUCTION: Initially considered experimental, liver transplantation (LT) has become the treatment of choice for the patients with end-stage liver diseases. MATERIAL AND METHODS: Between April 2000 and October 2009, 200 LTs (10 reLTs) were performed in 190 patients, this study being retrospective. There were transplanted 110 men and 80 women, 159 adults and 31 children with the age between 1 and 64 years old (mean age--39.9). The main indication in the adult group was represented by viral cirrhosis, while the pediatric series the etiology was mainly glycogenosis and biliary atresia. There were performed 143 whole graft LTs, 46 living donor LTs, 6 split LTs, 4 reduced LTs and one domino LT RESULTS: The postoperative survival was 90% (170 patients). The patient and graft one-year and five-year survivals were 76.9%, 73.6% and 71%, 68.2%, respectively. The early complications occurred in 127 patients (67%). The late complications were recorded in 71 patients (37.3%). The intraoperative and early postoperative mortality rate was 9.5% (18 patients). CONCLUSIONS: The Romanian liver transplantation program from Fundeni includes all types of current surgical techniques and the results are comparable with those from other international centers.

Robotic spleen-preserving distal pancreatectomy. A case report.

Distal pancreatectomy (DP) is the removal of the pancreatic tissue at the left side of the superior mesenteric vein and it is traditionally approached by an open or laparoscopic exposure. Preservation of the spleen is optional but appears to have a better immunological outcome. We present the case of a 53-year old patient with a 2.4/2.2 tumor located in the tail of the pancreas, with high tumour marker values for whom we decided to perform a robotic spleen-preserving distal pancreatectomy (RSPDP). The postoperative outcome was satisfactory. In conclusion, we recommend this type of approach for small pancreatic tail lesions.

Robotic radical hysterectomy with pelvic lymphadenectomy: our early experience.

INTRODUCTION: Robotic surgery overcomes some limitations of laparoscopic surgery for prostate, rectal and uterine cancer. In this study we analyze the feasibility of robotic radical hysterectomy with pelvic lymphadenectomy in gynecological cancers in a developping program of robotic surgery. MATERIAL AND METHODS: This prospective study started the 1st of March 2008. Since then, 250 cases of robotic surgery were performed out of which 29 cases addressed gynecological conditions. We selected all radical interventions summing up to 19 cases. RESULTS: Our final group consisted of 19 patients, a gedbetween 30 and 78 years old, with an average age of 53.22 years (+/- 10.03). Twelve patients were diagnosed with cervical cancer, the rest of them with endometrial cancer. Mean operative time was 180 +/- 23.45 min. Oral intake were started the next day after the operation and the patients were discharged 3.5 (+/- 1.2) days postoperatively. There were 3 urinary complications in patients with tumors adherent to the urinary bladder. CONCLUSIONS: We believe that robotic radical hysterectomy with pelvic lymphadenectomy in gynecological cancers is a rapid, feasible, and secure method that should be used whenever available. However further prospective studies and late follow-up results are needed in order to fully assess the value of this new technology.

[Insulinoma of the pancreas: analysis of a clinical series of 30 cases]. / Insulinomul pancreatic--analiza unei serii clinice de 30 de cazuri.

UNLABELLED: Insulinoma is the most frequent neuroendocrine pancreatic tumor and is the main cause for hypoglicemia due to endogenous hyperinsulinism. We performed an analysis of a clinical series in order to study the clinical and biological spectrum of presentation, the preoperatory imagistic diagnosis and results of the surgical approach. Between 1986-2009, 30 patients with symptoms suggesting an insulinoma were hospitalized in our department. Preoperatory localization of insulinomas was possible in 16 patients. The most sensitive imagistic methods were ecoendoscopy and magnetic resonance. Intraoperatory ultrasound was performed in 16 patients and its sensitivity in detection of insulinomas was 93%; the combination between intraoperative ultrasound and manual exploration of pancreas by the surgeon reached a 100% sensitivity. Before the intraoperatory ultrasound was used the tumor excision was predominantly done by extensive pancreatic resection, while after this was available in our centre more conservative (enucleo-resection) procedures were chosen. In 1 patient the resection was done by laparoscopy, and in 1 patient by robotic surgery. The dimensions of the tumor were less than 2 cm in most of the patients; 2 had nesidioblastosis and 2 had multiple insulinomas; all 28 patients proved to have benign insulinomas at histological specimens. Following surgery, the symptoms disappear in all patients. The most common complication following extensive pancreatic resections was acute pancreatitis, while after enucleation pancreatic fistula occurred more frequently. CONCLUSIONS: Due to small dimensions, the preoperative diagnosis of insulinomas is usually difficult, ecoendoscopy being the most sensitive method. Intraoperative ultrasound is essential for insulinoma localization and for chosing the optimal type of excision. Enucleation is the resection method to be chosen whenever this it is technical possible. In benign insulinomas the prognosis is excellent, surgical resection being curative in all cases.

Transplantation of mesenchymal stem cells cultured on biomatrix support induces repairing of digestive tract defects, in animal model.

Transplanted mesenchymal stem cells (MSCs) appear to play a significant role in adult tissue repair. The aim of this research was to obtain MSCs enriched, three dimensional (3D) patches for transplant, and to test their ability to induce repair of iatrogenic digestive tract defects in rats. MSCs were obtained from human and rat bone marrow, cultured in vitro, and seeded in a collagen-agarose scaffold, where they showed enhanced viability and proliferation. The phenotype of the cultured cells was representative for MSCs (CD105+, CD90+, and CD34-, CD45-, CD3-, CD14-). The 3D patch was obtained by laying the MSCs enriched collagen-agarose scaffold on a human or swine aortic fragment. After excision of small portions of the rat digestive tract, the 3D patches were sutured at the edge of the defect using micro-surgical techniques. The rats were sacrificed at time-points and the regeneration of the digestive wall was investigated by immunofluorescence, light and electron microscopy. The MSCs enriched 3D patches were biocompatible, biodegradable, and prompted the regeneration of the four layers of the stomach and intestine wall in rats. Human cells were identified in the rat regenerated digestive wall as a hallmark of the transplanted MSCs. For the first time we constructed 3D patches made of cultured bone marrow MSCs, embedded into a collagen-rich biomatrix, on vascular bio-material support, and transplanted them in order to repair iatrogenic digestive tract defects. The result was a complete repair with preservation of the four layered structure of the digestive wall.

Total laparoscopic radical hysterectomy with pelvic lymphadenectomy for endometrial cancer.

The surgical treatment of endometrial cancer is still a matter of debate. Two of the most controversial issues are the beneficial effect of lymphadenectomy and the feasibility of laparoscopy. The aim of the case report was to describe the feasibility of total laparoscopic radical hysterectomy with pelvic lymphadenectomy in a 56-years-old Caucasian woman diagnosed with endometrial cancer. After a CO2 pneumoperitoneum was created the peritoneum was incised cranially to the para-colic fossa just above the external iliac vessels until the psoas muscle is visualized. The external iliac vessels were identified and lymph nodes from the anterior and the medial surface were removed until the iliac bifurcation and placed in an Endo-bag. The procedure continued with the identification of the hypo-gastric and the umbilical artery which were pulled medially in order to open the obturator fossa and remove the lymphatic tissue superior to the obturator nerve. The next step was the opening of the para-vesical and pararectal spaces by using blunt dissection; this maneuver was facilitated by pulling the uterine fundus towards the opposite direction with the uterine manipulator. The parametrium being isolated between the two spaces can be safely divided. At the superior limit of the parametrium the uterine artery is identified and divided at its origin. Thereafter, by placing the uterine fundus in median and posterior position, the vesicouterine peritoneal fold was opened by scissors and a bladder dissection from the low uterine segment down to the vagina was performed. Then the ureter is dissected, freed from its attachments to the parametria and de-crossed from the uterine artery down to its entry into the bladder. Next the rectovaginal space is opened and the utero-sacral ligaments divided; this allows the division of para-vaginal attachments. The vagina is sectioned and the specimen is extracted transvaginally. Then the vaginal stump was sutured by laparoscopy. Total laparoscopic radical hysterectomy with pelvic lymphadenectomy was not associated with an increased operative time or blood loss and appears to be a feasible alternative to conventional surgical approach in patients with endometrial carcinoma.

Hepatocellular carcinoma in Riedel's lobe.

We present a rare case of 65-year female with right abdominal mass and abdominal discomfort; a combination of Doppler ultrasonography, computed tomography and laparotomy was utilized to make a diagnosis of tumoral Riedel's lobe. In our case, laparotomy with resection of Riedel's lobe was the proper therapeutical solution.