Peter Kujath

Ordinary colorectal adenocarcinomavs. primary colorectal signet-ring cell carcinoma

PURPOSE This study contributes to the characterization of primary colorectal signet-ring cell cancer in contrast to ordinary colorectal carcinoma. Primary colorectal signet-ring cell cancer is a rare but distinctive primary neoplasm of the large bowel with still-controversial clinicopathologic features. METHODS Clinicopathologic features and survival data are evaluated in comparison with those of the ordinary colorectal adenocarcinoma (non-signet colorectal carcinoma) in a retrospective study matched for age, gender, grade, and stage. RESULTS In a series of 1,600 consecutive colorectal cancer patients since 1979, 14 patients (0.88 percent) with a signet-ring cell cancer were identified. Gender ratio was balanced, and mean age was 67.5 years. The majority of patients had an advanced tumor stage at the time of diagnosis (57.1 percent Stage IV and 35.7 percent Stage III). Median survival time was only 16 months. In a study matched for age, gender, grade, and stage, a lower survival rate was found for patients with signet-ring cell cancer, but the difference did not reach statistical significance. In contrast to non-signet colorectal carcinoma, signet-ring cell cancer was characterized by a significantly higher incidence of peritoneal tumor spread (64.3 percent) and a lower incidence of hepatic metastases (14.3 percent). CONCLUSIONS Signet-ring cell cancer represents a rare but distinctive primary neoplasm of the large bowel. It is frequently diagnosed in an advanced tumor stage, thus showing an overall poorer prognosis than nonsignet colorectal carcinoma. Usually only palliative surgery is possible. A high incidence of peritoneal seeding and a low incidence of hepatic metastasis is characteristic of signet-ring cell cancer.PURPOSE: This study contributes to the characterization of primary colorectal signet-ring cell cancer in contrast to ordinary colorectal carcinoma. Primary colorectal signetring cell cancer is a rare but distinctive primary neoplasm of the large bowel with still-controversial clinicopathologic features. METHODS: Clinicopathologic features and survival data are evaluated in comparison with those of the ordinary colorectal adenocarcinoma (nonsignet colorectal carcinoma) in a retrospective study matched for age, gender, grade, and stage. RESULTS: In a series of 1,600 consecutive colorectal cancer patients since 1979, 14 patients (0.88 percent) with a signet-ring cell cancer were identified. Gender ratio was balanced, and mean age was 67.5 years. The majority of patiens had an advanced tumor stage at the time of diagnosis (57.1 percent Stage IV and 35.7 percent Stage III). Median survival time was only 16 months. In a study matched for age, gender, grade, and stage, a lower survival rate was found for patients with signet-ring cell cancer, but the difference did not reach statistical significance. In contrast to nonsignet colorectal carcinoma, signet-ring cell cancer was characterized by a significantly higher incidence of peritoneal tumor spread (64.3 percent) and a lower incidence of hepatic metastases (14.3 percent). CONCLUSIONS: Signet-ring cell cancer represents a rare but distinctive primary neoplasm of the large bowel. It is frequently diagnosed in an advanced tumor stage, thus showing an overall poorer prognosis than nonsignet colorectal carcinoma. Usually only palliative surgery is possible. A high incidence of peritoneal seeding and a low incidence of hepatic metastasis is characteristic of signetring cell cancer.

New Insights into the Epidemiology and Etiology of Fournier’s Gangrene: A Review of 33 Patients

AbstractBackground:Fournier’s gangrene is a necrotizing fasciitis involving the perineal and genital regions. Even today, this often polymicrobial infection still carries a high mortality rate and continues to be a major challenge to the medical community. The purpose of this study was to report our experience with this condition and to compare it with those reported in published studies. We also introduce our approach to treatment.Methods:We analyzed data from 33 patients with Fournier’s gangrene who were managed in our hospital from 1996 to 2007, focusing on patient gender, age, etiology, predisposing conditions, comorbidities, bacteriology, sepsis, blood results, mortality, and spread of gangrene.Results:18 (54.5%) of the 33 patients had been referred to our department by smaller district hospitals. The patient cohort consisted of 23 men and ten women with a median age of 59 years (range 40–79 years). The median time between the onset of symptoms and progression to gangrene was 6 days (range 2–28 days). An underlying cause was identified in 27 patients (81.8%). The commonest etiological events were perianal and perirectal abscesses (n = 13; 39.4%). Predisposing factors included diabetes mellitus in 12 cases (36.4%), chronic alcoholism in ten cases (30.3%), immunosuppression in six cases (18.2%), and prolonged immobilization in five cases (15.2%). 17 patients (51.5%) had a body mass index (BMI) of 25 or higher, and 13 patients (39.4%) had a BMI of 30 or higher. Positive cultures were obtained in 30 cases (90.9%). In 26 cases (78.8%), multiple microorganisms were recovered, including nine cases (27.3%) with both aerobes and anaerobes. Sepsis was present in 26 patients (78.8%). The mortality rate was 18.2%.Conclusion:Fournier’s gangrene remains a major challenge with a high mortality. Our results suggest that women are more commonly affected than has generally been assumed. Contrary to published reports, we found that anorectal sources appear to account for more cases of Fournier’s gangrene than urological sources.

Fournier's gangrene: vacuum-assisted closure versus conventional dressings

BACKGROUND Fourniers gangrene is a fulminant and destructive inflammation of the scrotum, penis, and perineum. The objective of this study was to compare 2 different approaches to wound management after aggressive surgical debridement. METHODS Data from 35 patients with Fourniers gangrene were prospectively collected (1996-2007). Once the patients were stabilized following surgery, they were treated with either daily antiseptic (polyhexanide) dressings (group I, n = 16) or vacuum-assisted closure (VAC) therapy (group II, n = 19). RESULTS The mean age of the patients was 58.2 years in group I and 57.2 years in group II. In both groups, the most common predisposing conditions were diabetes mellitus, chronic alcoholism, and obesity. Escherichia coli, streptococcal species, Pseudomonas aeruginosa, and Staphylococcus aureus were the most frequently isolated organisms. Length of hospital stay was 27.8 days +/- 27.6 days (mortality: 37.5%) in group I and 96.8 days +/- 77.2 days (mortality: 5.3%) in group II. Enterostomies were performed in 43.8% of group I patients and in 89.5% of group II patients. CONCLUSIONS VAC was associated with significantly longer hospitalization and lower mortality. A partial explanation is that some patients with severe sepsis died within the first 3 days after admission and thus could not undergo vacuum therapy. Since our clinical experience has shown that vacuum dressings are particularly effective in the management of large wounds, we use VAC primarily for this indication despite the considerable material requirements involved.

Tumorzelldissemination in das Knochenmark und in die Peritonealhohle eine immunzytochemische Untersuchung an Patienten mit einem Magen- oder kolorektalen Karzinom

The tumor spread and the radicality of surgical resection are the most important facts in a patients prognosis. In spite of curative tumor resection many patients die from metastases or local tumor recurrence. One possible reason is early dissemination of tumor cells which cannot be detected with clinical methods of examination. For this reason the aim of our study was to examine both bone marrow and peritoneal lavage for disseminated tumor cells with an immunocytochemical technique in patients with a gastrointestinal carcinoma. We also wanted to find out whether there was any correlation between the incidence of tumor cell detection and the TNM classification, staging and tumor grading and whether disseminated tumor cells have any prognostic significance. Our study included 54 patients who underwent surgery in our clinic for a carcinoma of the stomach (20 patients) or the colorectum (34 patients) from November 1993 to December 1994. At the beginning of the operation bone marrow had been taken from the iliac spine, and the abdomen was irrigated with 1000 ml saline solution immediately after laparotomy or laparoscopy. After cell separation with Ficoll density centrifugation 5 × 105 cells were applied per slide by a cytospin technique. For detection of the tumor cells we used the APAAP technique and the following monoclonal antibodies: KL1, CK2, anti-CEA, 17-1A (bone marrow) and Ber-EP4, B72.3, anti-CEA and 17-1A (peritoneal lavage). Altogether 77% of all patients had tumor cells in the bone marrow and 69% in peritoneal lavage fluid. It was possible to detect tumor cells in bone marrow (67%) and peritoneal lavage fluid (25%) even of patients with T1 tumors. The percentage increased with depth of wall infiltration. There was a marked difference in bone marrow aspirates between patients with lymph-node-negative tumors (N0) and those with lymph-node-positive tumors (N+): 65% had tumor cells in N0 and 85% in N+ stages. This trend was also seen in patients with (M1) and without (M0) metastases, in both bone marrow aspirates and peritoneal lavage fluid. In bone marrow there was a good correlation of tumor cells with staging, but in peritoneal lavage fluid this was not so. Finally, we detected tumor cells more often in bone marrow and peritoneal lavage fluid of patients with poorly differentiated tumors (G3) or diffuse Laurén type than in patients with moderately differentiated tumors (G2) or intestinal Laurén type. After a median follow-up period of 12.5 months patients with disseminated tumor cells had a lower survival rate than patients without tumor cells.ZusammenfassungDie Tumorausdehnung und die Radikalität des chirurgischen Eingriffs sind für die Prognose eines Patienten von großer Bedeutung. Trotz kurativer Resektion des Tumors versterben jedoch viele Patienten an den Folgen der Fernmetastasierung oder einem lokalen Rezidiv. Die Ursache dafür könnte eine frühe Dissemination von Tumorzellen sein, welche derzeit mit den herkömmlichen klinischen Untersuchungsmethoden noch nicht erfaßt werden kann. Aus diesem Grunde war es das Ziel unserer Studie, das Knochenmark und die Peritonealspülflüssigkeit von Patienten mit einem gastrointestinalen Karzinom auf Tumorzellen mit immunzytochemischer Technik zu untersuchen. Außerdem wollten wir wissen, ob eine Korrelation zur TNM-Klassifikation, zum Tumorstadium und zum Tumordifferenzierungsgrad vorliegt und ob dem Tumorzellnachweis prognostische Relevanz zukommt. WirThe tumor spread and the radicality of surgical resection are the most important facts in a patients prognosis. In spite of curative tumor resection many patients die from metastases or local tumor recurrence. One possible reason is early dissemination of tumor cells which cannot be detected with clinical methods of examination. For this reason the aim of our study was to examine both bone marrow and peritoneal lavage for disseminated tumor cells with an immunocytochemical technique in patients with a gastrointestinal carcinoma. We also wanted to find out whether there was any correlation between the incidence of tumor cell detection and the TNM classification, staging and tumor grading and whether disseminated tumor cells have any prognostic significance. Our study included 54 patients who underwent surgery in our clinic for a carcinoma of the stomach (20 patients) or the colorectum (34 patients) from November 1993 to December 1994. At the beginning of the operation bone marrow had been taken from the iliac spine, and the abdomen was irrigated with 1000 ml saline solution immediately after laparotomy or laparoscopy. After cell separation with Ficoll density centrifugation 5 x 10(5) cells were applied per slide by a cytospin technique. For detection of the tumor cells we used the APAAP technique and the following monoclonal antibodies: KL1, CK2, anti-CEA, 17-1A (bone marrow) and Ber-EP4, B72.3, anti-CEA and 17-1A (peritoneal lavage). Altogether 77% of all patients had tumor cells in the bone marrow and 69% in peritoneal lavage fluid. It was possible to detect tumor cells in bone marrow (67%) and peritoneal lavage fluid (25%) even of patients with T1 tumors. The percentage increased with depth of wall infiltration. There was a marked difference in bone marrow aspirates between patients with lymph-node-negative tumors (N0) and those with lymph-node-positive tumors (N+): 65% had tumor cells in N0 and 85% in N+ stages. This trend was also seen in patients with (M1) and without (M0) metastases, in both bone marrow aspirates and peritoneal lavage fluid. In bone marrow there was a good correlation of tumor cells with staging, but in peritoneal lavage fluid this was not so. Finally, we detected tumor cells more often in bone marrow and peritoneal lavage fluid of patients with poorly differentiated tumors (G3) or diffuse Lauren type than in patients with moderately differentiated tumors (G2) or intestinal Lauren type. After a median follow-up period of 12.5 months patients with disseminated tumor cells had a lower survival rate than patients without tumor cells.

Expression of p53 and mdm2 mRNA and protein in colorectal carcinomas

The aim of our study was to investigate the expression of p53 and mdm2 mRNA and protein in colorectal adenocarcinoma. For the detection of mRNA, 60 fresh frozen human tumour samples and 12 samples of corresponding normal tissue were examined. After total RNA extraction, reverse transcription (RT) was performed followed by cDNA amplification with specific primers using RT-polymerase chain reaction (PCR). Immunohistochemical detection of protein was examined in 81 formalin-fixed and paraffin-embedded human tumour specimens as well as 15 samples of adjacent normal colorectal tissue. p53 mRNA was detected in 80% (48/60) of the tumours and in 67% (8/12) of normal tissue samples; 87% (52/60) of tumours had mdm2 mRNA in contrast to only 17% (2/12) of normal tissue specimens. Nuclear p53 protein expression was observed in 52% (42/81) of the tumour specimens and in none of the 15 normal specimens, whereas mdm2 protein was found in the nucleus (31%, 25/81) and also in the cytoplasm (86%, 70/81) of tumour samples. In normal tissue, mdm2 protein expression was only observed in the cytoplasm (13%, 2/15) and not in the nucleus. There was a significant correlation between coexpression of p53 and mdm2 protein and the occurrence of lymph node metastases (P = 0.03) as well as between p53 protein expression and the occurrence of distant metastases (P = 0.007). Additionally, significant associations were found between p53 mRNA and p53 protein, p53 mRNA and mdm2 mRNA or protein, and also between mdm2 mRNA and mdm2 protein expression, supporting the existence of a regulatory mechanism involving p53 and mdm2.

High Frequency of Aneuploidy Defines Ulcerative Colitis-Associated Carcinomas: A Prognostic Comparison to Sporadic Colorectal Carcinomas

Objective:Aneuploidy is an independent risk factor for forthcoming carcinogenesis in ulcerative colitis (UC). An inferior prognosis of patients with ulcerative colitis-associated colorectal cancer (UCC) compared with those with sporadic colorectal cancer (SCC) has been reported, but remains controversial. This prompted us to investigate if aneuploidy can be observed in UCCs as frequently as in their sporadic counterpart and if aneuploidy per se might be a driving feature of poor prognosis in UCC. Background Data:We obtained clinical follow-up for 257 SCC patients (average observation time 57 months) and 31 UCC patients (51 months). Touch preparation slides or tissue sections were prepared of all 288 carcinomas for ploidy analysis. Methods:Ploidy status was assessed for 260 SCCs and 31 UCCs by image cytometry and correlated to clinical features. Survival data were analyzed using Kaplan-Meier estimates. Results:Aneuploidy was detected in 74.6% of SCCs and in all 31 UCCs. Logistic regression analysis yielded age (odds ratio [OR], 1.05; 95% CI, 1.02–1.09; P = 0.003) and aneuploidy (OR, 4.07; 95% CI, 1.46–11.36; P = 0.007) as independent prognostic factors for R0-resected patients devoid of metastases. Diploid SCCs had a more favorable 5-year survival (88.2%) than aneuploid SCCs (69.0%) and UCCs (73.1%) (P = 0.074). Conclusions:UC-associated carcinomas presented aneuploidy at significantly higher frequency than sporadic colorectal carcinomas (P < 0.0006). UCCs and aneuploid SCCs share a similar prognosis inferior to that of diploid SCCs. Aneuploidy proved to be the strongest independent prognostic marker for R0-resected colorectal cancer patients overall.

Survival of diabetes patients with major amputation is comparable to malignant disease.

Introduction: Almost all studies on diabetic foot syndrome focused on prevention of amputation and did not investigate long-term prognosis and survival of patients as a primary outcome parameter. Methods: We did a retrospective cohort study including 314 patients who had diabetic foot syndrome and underwent amputation between December 1995 and January 2001. Results: A total of 48% of patients received minor amputation (group I), 15% only major amputation (group II) and 36% initially underwent a minor amputation that was followed by a major amputation (group III). Statistically significant differences were observed in comparison of the median survival of group I to group II (51 vs 40 months; p = 0.016) and of group II to group III (40 vs 55 months; p = 0.003). Discussion: The prognosis of patients with major amputation due to diabetic foot syndrome is comparable to patients with malignant diseases. Vascular interventions did not improve the individual prognosis of patients.

Cold-plasma coagulation in the treatment of malignant pleural mesothelioma: results of a combined approach

Malignant pleural mesothelioma is on a continuous rise throughout the Western countries. It is associated with asbestos fibre exposition in the past. Surgical approaches include extrapleural pneumonectomy and pleurectomy/decortication (P/D). We investigated the feasability of the implementation of cold-plasma coagulation (CPC) on the pleura, pericardium and diaphragm into an established therapeutic algorithm consisting of P/D and hyperthermic intrathoracal chemoperfusion (HITHOC) therapy. The underlying rationale was the prevention of cardiotoxic effects during HITHOC as well as accidental translocation of malignant cells to the abdomen. CPC was done as part of a multimodal therapy in stage III mesothelioma patients. Histologic examinations of pleural excisates after CPC were done. The patients were followed up in three-month intervals. Neither parenchymal fistulas, nor cardiotoxic effects were observed. The histologic examination of the pleural excisates showed complete predictable necrosis. Moreover, until now (median time after operation 1 year) no relapse of the disease was observed. CPC proved to be a safe technique when used on the pleura, pericardium and diaphragm. We consider our trial as a pilot-study. To evaluate potential survival benefits using this technique larger trials are mandatory.

Hydro-Jet–Assisted Pneumonectomy: A New Technique in a Porcine Model

BACKGROUND AND OBJECTIVES Hydro-jet technology has long been used to cut various materials, such as metal and wood, in the industrial field. In the medical field, this technology has been applied successfully in selective cutting of the parenchyma of the liver. However, to our knowledge, no data are available on the use of the hydro-jet technique for pneumonectomy. The purpose of this study was to evaluate a new dissection technique in which a high-pressure water stream (hydro-jet) and a new dissection probe for pulmonary resection are used. METHODS Thirty pigs underwent right pneumonectomy. Pigs were randomized to either the conventional or hydro-jet-assisted dissection technique. The feasibility of this technique and the features of surgical dissection were evaluated and compared between the two groups. RESULTS Pneumonectomy was successful in all animals. The mean operative times were 55 and 65 minutes and the mean volumes of blood loss were 37 and 65 mL for the hydro-jet and conventional dissection techniques, respectively. Complications included vascular injury in 6% and 20% of cases with the hydro-jet and conventional techniques, respectively. The use of hydro-jet for pneumonectomy had clear technical advantages over the conventional dissection. Hydro-jet resulted in a selective dissection of fibrous and connective tissue, preserving blood vessels for later ligation. Therefore, the dissection was performed in a relatively bloodless field. The ease of dissection with the bent-tip dissector represents another advantage. The continuous water flow allows a clear view for the operator. CONCLUSIONS This study shows that hydro-jet dissection represents an excellent alternative to the conventional technique for pulmonary resection. The improved anatomic dissection combined with an almost bloodless operating field secondary to continuous water flow may decrease dissection-related complications.

Thoracic surgery in the elderly – co-morbidity is the limit

A retrospective chart review was performed in 242 consecutive patients aged 65 years or older who were treated in an academic surgical centre between January 2004 and July 2007. A total of 249 thoracic procedures were performed in 242 patients, of whom 143 were men and 99 women with a mean age of 69.9 years (range 65-92). Overall operative mortality was 2.4%, rising to 26.4% in emergency patients. Negative predictors for perioperative mortality were: American Society of Anesthesiology (ASA) class 4, pre-existing kidney failure, leucocytosis, low haemoglobin, elevated C-reactive protein, diabetes mellitus and emergency surgery. In addition, the risk of major and minor complications resulting in a prolonged hospital stay was increased in emergency patients, patients with multiple co-morbidities and ASA class 3 or 4. Appropriate thoracic surgery can be offered to the elderly with an acceptable level of perioperative morbidity and mortality. Regardless of age, a high degree of co-morbidity or emergency surgery are the main risk factors for perioperative mortality and/or prolonged hospital stay.