Absolute CT perfusion parameter values after the neoadjuvant chemoradiotherapy of the squamous cell esophageal carcinoma correlate with the histopathologic tumor regression grade.

PURPOSE: To analyze value of the computed tomography (CT) perfusion imaging in response evaluation of the esophageal carcinoma to neoadjuvant chemoradiotherapy (nCRT) using the histopathology as reference standard. METHODS: Forty patients with the squamous cell esophageal carcinoma were re-evaluated after the nCRT by CT examination, which included low-dose CT perfusion study that was analyzed using the deconvolution-based CT perfusion software (Perfusion 3.0, GE). Histopathologic assessment of tumor regression grade (TRG) according to Mandard's criteria served as reference standard of response evaluation. Statistical analysis was performed using Spearman's rank correlation coefficient (r(S)) and Kruskal-Wallis's test. RESULTS: The perfusion CT parameter values, measured after the nCRT in the segment of the esophagus that had been affected by neoplasm prior to therapy, significantly correlated with the TRG: blood flow (BF) (r(S)=0.851; p<0.001), blood volume (BV) (r(S)=0.732; p<0.001) and mean transit time (MTT) (r(S)=-0.386; p=0.014). Median values of BF and BV significantly differed among TRG 1-4 groups (p<0.001), while maximal esophageal wall thickness did not (p=0.102). Median BF and BV were gradually rose and MTT decreased as TRG increased, from 21.4 ml/min/100 g (BF), 1.6 ml/100 g (BV) and 8.6 s (MTT) in TRG 1 group, to 37.3 ml/min/100 g, 3.5 ml/100 g and 7.5 s in TRG 2 group, 81.4 ml/min/100 g, 4.1 ml/100 g and 3.8 s in TRG 3 group, and 121.1 ml/min/100 g, 4.9 ml/100 g and 3.7 s in TRG 4 group. In all 15 patients who achieved complete histopathologic regression (TRG 1), BF was <30.0 ml/min/100 g. CONCLUSIONS: CT perfusion could improve the accuracy in response evaluation of the esophageal carcinoma to nCRT.

Micrometastasis of hypopharyngeal cancer.

PURPOSE: The aim of this study is to estimate the incidence and clinical impact of lymph node micrometastases in hypopharyngeal squamous cell cancer (HSCC). MATERIALS AND METHODS: In this retrospective study, we enrolled 58 patients who have undergone surgery for HSCC (between January 2004 and January 2011). Pharyngolaryngectomy and oesophagectomy with selective bilateral neck dissection was performed in all patients. Based on standard histological examination, 17 patients met N0 and 8 patients met N1 criteria and were further evaluated for the presence of micrometastases and isolated tumour cells (ITC). Following immunohistochemical analysis, the patients were grouped according to the presence of micrometastases and ITCs. RESULTS: In the pN0 group, cytokeratin-positive cells were detected in five patients, and they were marked as N0/CK+. Among these five patients, two were found to harbour micrometastases and ITCs, whilst in three, only ITCs were found. Two patients (11.75 %) were upstaged to pN1. The patients marked as N0/CK+ had a statistically significant worse overall survival rates than pN0 patients with tissue samples read as negative for cytokeratin immunostaining (p = 0.019, p < 0.05). In the pN1 group, cytokeratin-positive cells were detected in two patients, with one patient showing micrometastases and ITC, and the other showing ITC only. One patient was upstaged to pN2. CONCLUSION: Patients with lymph node micrometastases and ITC had worse overall survival rates, which may indicate that more aggressive post-operative treatment regimens should be considered for these HSCC patients.

Is there a correlation between molecular markers and response to neoadjuvant chemoradiotherapy in locally advanced squamous cell esophageal cancer?

PURPOSE: To evaluate the expression of epidermal growth factor receptor (EGFR), p53, p21 and thymidylate synthase (TS) in a pretherapy biopsy specimen of locally advanced squamous cell esophageal cancer and correlate these markers with response to neoadjuvant chemoradiotherapy. METHODS: Sixty-two patients with histopathologically proven locally advanced (T3 or greater) squamous cell esophageal cancer were enrolled. The expression of EGRF, p53, p21 and TS markers was assessed with immunohistochemistry. Semiquantitative assessment of expression of these markers was performed based on the percent of the stained cells. Radiotherapy (45-50.4 Gy) was delivered concomitantly with 5-fluorouracil (5-FU)/leucovorin (LV)/cisplatin (CIS) chemotherapy. Five to 6 weeks after chemoradiation, response to treatment was assessed. Medically fit and operable patients were operated. The resected material underwent histopathological evaluation of tumor expansion, histological classification after initial multimodality treatment (yp TNM), residual status and tumor regression grade (TRG). RESULTS: Out of 62 patients enrolled, 41 (66%) were evaluated for molecular markers. Clinical response rate was 43.9%. Out of 41 patients, 12 (29%) underwent surgery. TRG 1 was noted in 58% of the patients. In a pretherapy tumor specimen, positive expression was noted in 80, 90, 80 and 71% for EGFR, p53, p21 and TS, respectively. We noted no statistically significant difference neither between tumor marker expression and clinical response to chemoradiation, nor between tumor marker expression and TRG. CONCLUSION: We registered no difference in response to treatment between EGFR, TS, p21 and p53 positive and negative staining.

[Pathology and pathobiology of the oesophageal carcinoma].

Carcinoma of the oesophagus including carcinoma of gastro-oesophageal junction are rapidly increasing in incidence. During recent years there have been changes in the knowledge surrounding biology of the disease progression. Identification of dysplasia in mucosal biopsies is the most reliable pathologic indicator of an increased risk of development of squamous cell carcinoma and passes through the sequence of chronic esophagitis, low-grade and high-grade dysplasia and invasive carcinoma. Although Barrett's esophagus is a precursor to esophageal adenocarcinoma and have a well described sequence of carcinogenesis: the Barrett's metaplasia-dysplasia-adenocarcinoma sequence, not all patients with this disorder require intensive surveillance. The natural history of dysplasia is poorly understood, particularly in low-risk regions, and prospective follow-up studies are needed. Adjunctive methods to improve reproducibility, such as immunostaining for alpha-methylacyl-coenzyme A racemase (AMACR), show promise, but require confirmation in larger studies. In addition, several controversial methods such as detection of p16, p53, and DNA content abnormalities may help identify patients at particularly high risk for progression to cancer, but these techniques are not yet widely available for routine clinical application. More studies are needed to define other early nonmorphologic biomarkers for risk of squamous cell carcinoma. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as circumferential resection margin status and lymph node metastases are evaluated, including lymph node micrometastases and the sentinel node concept. With the rising use of multimodal treatments for oesophageal cancer it is important that the response of the tumour to this therapy can be carefully documented by histopathology.

The utility of 99mTc-EDDA/HYNIC-TOC scintigraphy for assessment of lung lesions in patients with neuroendocrine tumors.

UNLABELLED: Our aim was to assess clinical utility of 99mTc-EDDA/HYNIC-TOC scintigraphy for evaluation of lung lesions in patients with neuroendocrine tumors (NETs). Single photon emission computed tomography (SPECT) of the thorax and whole body scintigraphy were performed in 34 patients using 99mTc-EDDA/HYNIC-TOC. Visual assessment was complemented by semiquantitative evaluation based on tumor to non-tumor (T/NT) ratio. Clinical, laboratory, and histological findings served as the standard for comparison. Enhanced tracer uptake was observed on both SPECT and whole body scintigraphy in 29 of 34 patients (88% sensitivity). T/NT ratios were significantly higher on SPECT than whole body images (2.96+/-1.07 vs.1.70+/-0.43, p KEYWORDS: 99mTc-EDDA/Hynic-TOC, lung involvement of NETs, T/NT ratio.

Influence of long-term radiotherapy on symptoms and signs of locally advanced primary rectal cancer of distant localisation.

This study is a part of a clinical trial in preoperative radiotherapy of low rectal cancer, conducted as a prospective and partly retrospective clinical study. It was designed to estimate the influence of long-term radiotherapy on symptoms of locally advanced rectal cancer. We included 49 patients with T3/4 stage adenocarcinoma (diagnosis confirmed by clinical, pathological and CT examinations) of the lower two thirds of the rectum, who were treated with long-term radiotherapy (45 Gy in 20-25 fractions) and questioned for the presentation of symptoms before and after the treatment. The chief complaints of these patients were the presence of blood in stool, abdominal and pelvic pain, straining (tenesmus) and the alteration in bowel movement. We found a significant decrease in symptoms and signs of the illness after the radiotherapy as well as the improvement of the quality of life.

Ischaemic colitis--review.

Colonic ischaemia, commonly referred to as ischaemic colitis, is the most common type of intestinal ischaemia. The term "ischaemic colitis" was used by Marston (1966) with three typical patterns of injury described: transient reversible ischaemia, ischaemic ulcers with stricturing, and gangrenous ischaemic colitis. Dominant presenting symptoms were colicky abdominal pain, vomiting, bloody diarrhea, and hematochezia. Patients often have minimal signs on clinical examination. Most patients were diagnosed at colonoscopy. Two regions that are believed to be anatomically vulnerable to ischemic disease are "Griffith's point", at the splenic flexure and "Sudeck's critical point", of the Drummond marginal artery. Clinically, ischaemic colitis is classified as non-gangrenous or gangrenous. Non-gangrenous ischaemic colitis involves the mucosa and submucosa and accounts for 80-85 percent of all cases of ischaemic colitis. Non-gangrenous ischaemic colitis is further subclassified into transient, reversible ischaemic colitis with a less severe form of injury and chronic, non-reversible ischaemic colitis, which includes chronic colitis and stricture and has a more severe form of injury. Gangrenous ischaemic colitis accounts for the remaining 15-20 percent of cases and manifests as the most seve-re form of injury. It includes acute fulminant ischaemia with transmural infarction that may progress to necrosis and death. Specific indications for operation include peritonitis, perforation, recurrent fever or sepsis, clinical deterioration in patients refractory to me-ical management. Relative indications include fulminant colitis, massive hemorrhage, chronic protein losing colopathy, and symptomatic ischemic stricture.

Bimonthly 24 h infusion of high-dose 5-fluorouracil vs EAP regimen in patients with advanced gastric cancer. A randomized phase II study.

BACKGROUND: To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. PATIENTS AND METHODS: Histologically confirmed measurable advanced gastric cancer, age < 72 yr, ECOG performance status 0-2, no prior chemo- and radiotherapy, adequate organ functions. TREATMENT: EAP arm: doxorubicin (40 mg/m(2)), etoposide (360 mg/m(2)), and cisplatin (80 mg/m(2)) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m(2) 24 h infusion, biweekly. RESULTS: Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2-8), HD 5-FU arm 2 (1-8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16-50%]/HD 5-FU arm 10% (0-21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3-27], HD 5-FU arm 6 mo (4-25). CONCLUSIONS: Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.

Allantoic remnants presenting as a giant retroperitoneal cyst.

Urachal anomalies are usually found in early childhood or just after birth. These usually involve patent ductus urachus, urachal cyst, umbilical-urachal sinus or vesicourachal diverticulum. Very rarely are urachal anomalies found in adults, usully as an infected urachal cyst. We are presenting a case of surgically removed giant urachal retroperitoneal cyst that was found by chance during the abdominal ultrasound examination of a 22 year old man who was initially treated for idiopathic hypertension.

Lipomatosis of the ileocecal valve treated with right hemicolectomy as the consequence of an incomplete diagnostic procedure.

Lipomatosis is an excessive local or general accumulation of fat in the body. It is usually asymptomatic, but depending on localization and size it can cause the patient to experience various difficulties. It can occur within digestive system as a benign mass. We report a case of a 50 year old female presented with mild intestinal symptoms and anemia. She had a lipomatous change of ileocecal valve and due to positive fecal occult blood test, barium enema and incompletely performed colonoscopy was misdiagnosed as a malignant tumor and was treated accordingly.

[Gastrointestinal stromal tumors (GIST) of the stomach as a cause of upper gastrointestinal bleeding].

Gastrointestinal stromal tumors (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumor containing spindle cells (less commonly epitheloid cells or rarely both) and showing CD 117 (c-kit protein) positivity in more than 95% of cases. Although they may arise throughout the gut, the commonest site are stomach (60-70%), small intestine (20-30%), colorectum (5%) and esophagus (up to 5%). Rarely, GISTs develop in the retroperitoneum, omentum or mesentery. GIST originates from the intestinal cell of Cajal (ICC). ICCs are located in and around the myenteric plexus and are thought to function as intestinal pacemaker cells. Historicaly, GIST were often misclassified as leiomyomas or leiomyosarcomas. Subsequently, it has been determined that GISTs have distinct ultrastructural features and immunophenotypical markers compared with smooth muscle and smooth muscle tumors. GIST predominantly occur in middle aged and older patients, with no significant difference in the sex incidence. Data from the recent population study suggest an incidence of about 10-22 cases per million persons per year. Clinical presentation of GIST varies widely, and depends on tumor size and location. GISTs that caused symptoms tended to be larger with an average size of 6cm versus 2cm for asymptomatic GISTs. Symptoms are most commonly related to mass effect or bleeding. GISTs can grow very large before producing symptoms. Commonest symptom of gastric GIST is manifest or occult bleeding. Abudant, life-threateting bleeding that require urgent surgery is rare. For patient with primary, localized, nonmetastatic GIST, complete surgical resection represents the only chance for cure. Lymhadenectomy is not necessary, because lymph node metastasis is very rare. The 5 year survival rate in patients with resected primary GISTs ranges from 48-65%. Conventional chemotherapy and radiation therapy is ineffective in the treatment of GIST. Imatinib mesilate (a tyrosine kinase inhibitor) was confirmed to be effective against metastatic or unresectable GISTs.

[Gastrointestinal gastric tumor (GIST) as a cause of massive hemorrhage from the upper digestive tract].

Gastrointestinal stromal tumors GIST are rare mesenchymal tumors of the gastrointestinal tract characterized by expression of a receptor that activates tyrosine kinase called C- kit. Since malignant GIST has an extremely poor prognosis even after surgical resection. The developement of a tyrosine kinase inhibitor, STI571/imatinib mesylate/Gleevec, Glivec which inhibits the BCR-ABL, PDGF-R alpha, and C-Kit receptors, has changed the management of unresectable malignant GIST and has improved the survival of patients with metastaic disease. We report a 32 year old male patient with subcardiale gastric GIST and massive gastrointestinale bleeding. The patient underwent total gastrectomy, D2 lymphadenestomy, distal pancreatectomy and splenectomy on 02.02. 2004. Histopathology examination of the primary tumor revealed a strong C-Kit expression and CD 34 +++, Ki67 20 and so called "Pure GIST" was approved Liver metastasis was detected on ultrasound and CT 12 months later and segmentectomy S7 was performed on 23.03.2005. Postoperative course was uneventfull. HP examination--malignant 35 x 30 mm sarcoma like tumor of mesenchymal origin. The patient received adjuvant imatinib-mesylate Gleevec Novartis Pharma Basel 400 mg a day. The initial complete response to treatment continued to 24 monts postoperatively Imatinib is a recent and very promising tretemenextirpation remains the only curative treatment of malignant GIST as evideneced by our patient.

Incomplete operative removal of colorectal liver metastases followed by chemotherapy decreases survival in comparison to chemotherapy alone.

Metastatic colorectal carcinoma (CRC) has an inevitable fatal outcome except in a small percentage of selected patients, approximately 10-20%, with good prognosis after successful complete operative removal of the liver metastases. In patients not eligible for surgical resection of the liver metastases, chemotherapy is currently the only widely available treatment option. Controversy still exists about the criteria for operability of CRC liver metastases, and some patients, still undergo ineffective, i.e. unnecessary surgery. The aim of this paper is to analyse and compare the overall survival (OS) and time to progression (TTP) in patients who underwent incomplete removal of liver CRC metastases followed by chemotherapy, and patients treated with chemotherapy alone. Seventy-three patients with CRC liver metastases underwent incomplete operative removal of the metastases followed by FOLFIRI (Cohort A - 27 patients) or with FOLFIRI alone (Cohort B - 46 patients). Patients received FOLFIRI until progression. FOLFOX4 was used as second line chemotherapy. The median OS in Cohort A was 8 months, the median TTP was 5 months, and the response rate was 44%; the median OS in Cohort B was 19 months, the median TTP was 8m, and the response rate was 39%. There was a significant difference in OS and in TTP (p < 0.01) in favour of the chemotherapy alone group (B). Patients undergoing incomplete removal of the liver metastases had shorter survival and TTP in comparison with patients treated with chemotherapy alone.

Endoscopic removal of pedunculated leiomyoma of the sigmoid colon (case report and literature review of dignostic and treatment options).

Colonic leiomyoma are remarkably rare cause of colonic symptoms in clinical practice. They constitute only 3% of gastrointestinal leiomyomas and complete endoscopic removal of the tumour can be a problem because of its submucosal origin. We describe a 62-year female patient with a 8 mm leiomyoma of sigmoid colon that was successfully removed by conventional endoscopic snare electrocauterisation, without complications.

[The influence of Helicobacter pylori eradication on appearance of gastro-oesophageal reflux disease].

UNLABELLED: Gastro-oesophageal reflux disease (GERD) includes wide spectrum of symptoms caused by gastric acid regurgitation through the incompetent lower oesophageal sphincter in oesophagus. Etiopathogenesis of GERD is multifactorial. AIM OF THIS STUDY: to establish the relationship between Helicobacter pylori eradication and appearance or aggravating of present GERD. If this relationship exist, the aim is to estimate its level and clinical consequences. MATERIAL AND METHODS: 50 Helicobacter pylori positive patients with different endoscopic findings (ulcer disease, gastritis and non-ulcer dyspepsia) to whom eradication of Helicobacter pylori was done, were following next 6 months. Questionnaire, uppear GI endoscopy with verification changes of oesophagus in accordance to LA classification, histopathological examination of gastric and oesophageal mucosal biopsy specimens, and oesophageal manometry have been done to all patients. These examinations have been done before Helicobacter pylori eradication and one, three. six and none months after that. RESULTS: non statistical significant difference was found among the appearance or aggravating of present GERD in all patients during the following period (Cochran Q test; p=0,408). Non statistical significant difference was found among the endoscopic types of oesophagitis (LA classification) in all patients during the following 6 months (Friedman test; p=0,058). Non statistical significant difference was found among the changes of histopathological findings on distal oesophagus, too (Friedman test; p=0,217). CONCLUSION: Eradication od Helicobacter pylori infection does not cause the appearance or aggravating of present GERD. The presence of mildly form of GERD, or aggravating of present GERD is transitory, and haven't the statistical signification.

[The role of endoscopic ultrasound(EUS) in differential diagnosis of subepithelial oesophago-gastric lesions].

BACKGROUND: Endoscopic ultrasonography(EUS) allows high-resolution demonstration of the entire gut wall. The aim of the study was to clarify the usefulness of the EUS in differential diagnosis of upper gastro-intestinal subepithelail lesions(SEL). METHODS: From September 1998- March 2005, EUS was performed in 1600 patients. Among them, in 206pts (13%), this examination was carried out due to previous upper endoscopy, which revealed the suspicion to SEL or extraluminal compression. We studied the location, the size, echo pattern and originating layer of SEL. The results were compared with CT, angiography and operation with histology when possible. All EUS examinations were performed using Olympus GIF-130 videoecho-endoscope with 7,5/12MHz switchable radial probe. RESULTS: EUS accuracy in separating intramural masses from extraluminal compression was 96%(44/46). Among 160 pts with true SEL, in 95(59.3%), EUS revealed the existence of a stromal tumor arising from muscularis propria (92) or muscularis mucosae (3). The size of the tumor varied from 5-75mm; depth: 8-40mm. 33 patients were operated on. In 14/16(87%), the EUS diagnosis of benign stromal tumor was confirmed on operation. In 18/19(95%), EUS correctly disclosed the malignant tumor. EUS accuracy in predicting malignancy was 91.5%(32/35). Findings suggestive for malignancy were: size 40mm; inhomogenicity with microcysts and irregular outer margin. In 12 pts, EUS revealed lypoma. Abberant pancreas was correctly diagnosed in all 22pts. In 16 persons, EUS disclosed submucosal cysts: 6 of them were operated on and EUS diagnosis was confirmed in all. In 10 patients EUS visualized varices. The finding was confirmed on angiography. CONCLUSION: The EUS appears to be very effective in differential diagnosis of SEL in upper gastro-intestinal tract. Tumour size greater than 40mm, inhomomogenous echo pattern and irregular outer margin are very suggestive for malignancy.

The significance of lymphonodal micrometastasis in the patients with gastric adenocarcinoma.

Micrometastasis is defined as microscopical deposit of malignant cells, less than 2mm in diameter, separated from the primary tumor. This does not include discontinous growth in peritumoral region, but include microinolvement of regional lymph nodes. The literature on micrometastases, with special resperct to nodal micrometastasis, and their implications in gastric adenocarcinoma have been reviewed. Immunohistochemical detection offer the best accuracy for detection of nodal micrometastasis. Molecular techniques are more sensitive than method of immunohistochemical detection, but methods are compromised with false positive results caused by various sources of biological contamination. It is more than obvious that there is no definite agreement neither about risk factors, nor definitive clinical significance of micrometastatic node involvement in the patients with gastric adenocarcinoma. At present, the role of occult lymph node involvement proved its significance in two major fields: defining criteria for limited surgical dissection in the patients with early (sm) carcinoma in respect to detection of micrometastatic tissue in sentinel lymph node, and distinguishing the category of pN0 (Mi+) patients with potential benefit of postoperative adjuvant therapy.

[Peritoneal hepatobiliary cystadenoma--case report].

Hepatobiliary cystadenoma with mesenchymal stroma are infrequent form of cystic neoplasm that may be found in females only. It is difficult to reach correct diagnosis prior to surgery. We are presenting a case of 32 years-old female referred to our institution for revealing a cause of discomfort and pain in right subcostal region whereas peritoneal hepatobiliary cystadenoma has been determined. Abdominal ultrasonography and computerized tomography revealed cystic lesion adjacent to gall bladder, which was initially thought to be of echynococcal origin. At surgery, a mesenterial cystic neoplasm has been revealed, having a close contact with gall bladder, without signs of its infiltration. Pathophysiology discovered hepatobiliary cystadenoma with mesenchymal stroma. Pre-surgical differential diagnosis in hepatobiliary cystadenoma may be very difficult, especially if, like in the presented case, neoplasm has extra hepatic localization. Radical surgical excision is treatment of choice, concerning malignant potential of these neoplasms.