Michael M. Krausz

Inverse relation between levels of p27Kip1 and of its ubiquitin ligase subunit Skp2 in colorectal carcinomas

Previous studies have shown that low levels of p27Kip1, an inhibitor of G1 cyclin–dependent kinases, are associated with high aggressiveness and poor prognosis in a variety of cancers. Decreased levels of p27 are caused, at least in part, by acceleration of the rate of its ubiquitin‐mediated degradation. In cultured cells and cell‐free biochemical systems, it has been shown that p27 is targeted for degradation by a ubiquitin ligase complex that contains Skp2 (S‐phase kinase‐associated protein 2) as the specific substrate‐recognizing and rate‐limiting subunit. This investigation was undertaken to examine the possible relation between levels of p27 and of its specific ubiquitin ligase subunit Skp2 in human cancers.

Surgical aspects of gastrointestinal persimmon phytobezoar treatment

One hundred thirteen patients presented with gastrointestinal complications due to persimmon phytobezoars during a 3 year period. One hundred three patients had a history of persimmon ingestion. One hundred five patients had undergone previous gastric operation for duodenal ulcer, one patient underwent highly selective vagotomy, and seven patients had not undergone previous operation. An elevated temperature, leukocytosis, and decreased bowel sounds were typical early clinical manifestations of small bowel obstruction by persimmon phytobezoars. In 13 patients, gastric bezoars were found, in 20 patients, gastric and intestinal bezoars, and in 80 patients, intestinal bezoars. One hundred patients were treated surgically. In 14 of the 20 patients with concomitant gastric and intestinal phytobezoars, extraction of the bezoars was achieved by gastrotomy. Of the remaining six patients, it was achieved by intraoperative milking of the gastric bezoar into the small bowel in two patients and by conservative treatment in four patients. Of the 100 patients who presented with small bowel obstruction, 60 were treated by milking of the bezoar into the large bowel, 34 by enterotomy, and 6 by conservative therapy with intravenous fluids, gastric suction, and a water-soluble contrast meal. Small bowel resection of a gangrenous segment was necessary in two patients. Two patients died after operation because of sepsis and respiratory complications. Eleven of the 13 patients in whom postoperative wound infection developed underwent gastrotomy or enterotomy. We conclude that the treatment of choice of intestinal obstruction due to persimmon phytobezoars is milking of the bezoar into the large bowel without enterotomy. Preoperative or operative endoscopy should be performed in patients presenting with complications of gastrointestinal phytobezoars. Patients who have undergone gastric operation should be warned against the risk of persimmon ingestion.

Diagnosing Acute Appendicitis in Adults: Accuracy of Color Doppler Sonography and MDCT Compared with Surgery and Clinical Follow-Up

OBJECTIVEnThe objective of our study was to evaluate the accuracy of color Doppler sonography and contrast-enhanced MDCT in the diagnosis of acute appendicitis in adults and their utility as a triage tool in lower abdominal pain.nnnMATERIALS AND METHODSnWe reviewed the medical records of 420 consecutive adult patients, 271 women and 149 men, 18 years old or older, referred from the emergency department to sonography examination for clinically suspected acute appendicitis between January 2003 and June 2006. Patients underwent sonography of the right upper abdomen and pelvis followed by graded compression and color Doppler sonography of the right lower quadrant. CT was performed in 132 patients due to inconclusive sonography findings or a discrepancy between the clinical diagnosis and the sonography diagnosis. Sonography and CT reports were compared with surgery or clinical follow-up as the reference standard. Statistical analyses were performed by Pearsons chi-square test and cross-tabulation software.nnnRESULTSnSonography and CT correctly diagnosed acute appendicitis in 66 of 75 patients and in 38 of 39 patients, respectively, and correctly denied acute appendicitis in 312 of 326 and in 92 of 92 patients. Sonography was inconclusive in 17 of 418 cases and CT, in one of 132 cases. Sonography and CT allowed alternative diagnoses in 82 and 42 patients, respectively. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for sonography were 74.2%, 97%, 88%, 93%, and 92%, respectively, and for CT, 100%, 98.9%, 97.4%, 100%, and 99%.nnnCONCLUSIONnSonography should be the first imaging technique in adult patients for the diagnosis of acute appendicitis and triage of acute abdominal pain. CT should be used as a complementary study for selected cases.

Bowel Preparation Is Associated With Spillage of Bowel Contents in Colorectal Surgery

PURPOSEInfectious complications pose a significant cause of morbidity in colon and rectal surgery. This study was designed to assess the effect of bowel preparation on spillage of bowel contents into the peritoneal cavity during colorectal surgery, and its potential effect on the rate of postoperative infectious complications.METHODSThe quality of bowel preparation and the incidence of spillage of bowel contents were prospectively assessed in patients undergoing elective colon and rectal resection. The patients were followed for 30 days for postoperative infectious and noninfectious complications.RESULTSA total of 333 patients were included in this study, of which 181 did not receive mechanical bowel preparation. Intraoperative spillage of bowel contents occurred in 48 patients (14 percent), whereas in 285 patients (86 percent), spillage did not occur. There was a trend toward a higher rate of overall surgical infectious and noninfectious complications in patients who had spillage of bowel contents compared with patients without spillage; however, this difference was not statistically significant (18.7 vs. 11 percent, and 29 vs. 19 percent, respectively). Preoperative mechanical bowel preparation and colocolonic or colorectal anastomosis was associated with a higher rate of bowel contents spillage, although this difference did not reach statistical significance. Liquid colonic contents caused significantly higher rates of spillage.CONCLUSIONSSpillage of bowel contents into the peritoneal cavity during colon and rectal surgery may increase the rate of postoperative infectious complications. In addition, inadequate mechanical bowel preparation, leading to liquid bowel contents, increases the rate of intraoperative spillage.

Initial resuscitation of hemorrhagic shock

The primary treatment of hemorrhagic shock is control of the source of bleeding as soon as possible and fluid replacement. In controlled hemorrhagic shock (CHS) where the source of bleeding has been occluded fluid replacement is aimed toward normalization of hemodynamic parameters. In uncontrolled hemorrhagic shock (UCHS) in which bleeding has temporarily stopped because of hypotension, vasoconstriction, and clot formation, fluid treatment is aimed at restoration of radial pulse, or restoration of sensorium or obtaining a blood pressure of 80 mmHg by aliquots of 250 ml of lactated Ringers solution (hypotensive resuscitation). When evacuation time is shorter than one hour (usually urban trauma) immediate evacuation to a surgical facility is indicated after airway and breathing (A, B) have been secured (scoop and run). Precious time is not wasted by introducing an intravenous line. When expected evacuation time exceeds one hour an intravenous line is introduced and fluid treatment started before evacuation.Crystalloid solutions and blood transfusion are the mainstays of pre-hospital and in-hospital treatment of hemorrhagic shock. In the pre-hospital setting four types of fluid are presently recommended: crystalloid solutions, colloid solutions, hypertonic saline and oxygen-carrying blood substitutes. In unstable or unresponsive hemorrhagic shock surgical treatment is mandatory as soon as possible to control the source of bleeding.

Blunt and penetrating injuries caused by rubber bullets during the Israeli-Arab conflict in October, 2000: a retrospective study

BACKGROUNDnLow-velocity rubber bullets were used by Israeli police to control riots by Israeli-Arabs in early October, 2000. We aimed to establish the factors that contribute to severity of blunt and penetrating injuries caused by these missiles.nnnMETHODSnWe analysed medical records of 595 casualties admitted. We assessed relation of severity of injury to type of bullet, anatomical region of injury, and final outcome. Severity of injury was established by the abbreviated injury scale, and we calculated injury severity score.nnnFINDINGSn151 males and one female (age range 11-59 years) were included in the study, in whom 201 proven injuries by rubber bullets were detected. Injuries were distributed randomly over the body surface and were mostly located in the limbs (n=73), but those to the head, neck, and face (61), chest (39), back (16), and abdomen (12) were also frequently noted. 93 (61%) patients had blunt injuries and 59 (39%) penetrating ones. Severity of injury was dependent on ballistic features of the bullet, firing range, and anatomic site of impact. Two casualties died after a penetrating ocular injury into the brain and one died as a result of postoperative aspiration after a knee injury.nnnINTERPRETATIONnResistance of the body surface at the site of impact (elastic limit) is the important factor that ascertains whether a blunt or penetrating injury is inflicted and its severity. Inaccuracy of rubber bullets and improper aiming and range of use resulted in severe injury and death in a substantial number of people. This ammunition should therefore not be considered a safe method of crowd control.

Outcome of transanal endoscopic microsurgery and adjuvant radiotherapy in patients with T2 rectal cancer.

PurposeThe use of transanal endoscopic microsurgery for local excision of rectal cancer has recently gained wide acceptance as a valid and safe alternative for the surgical treatment of T1 tumors. The adequacy of such treatment for T2 tumors, however, is still controversial. This study was designed to evaluate our results with local excision of T2 cancers.MethodsPatients with T2 cancer admitted to our hospital between 1995 and 2005 were offered surgery by transanal endoscopic microsurgery if found medically unfit or were unwilling to undergo radical surgery. Patients who were preoperatively staged as T1 tumor but were found to be pathologically T2 also were included.ResultsOverall, we performed 59 transanal endoscopic microsurgery operations for rectal cancers, of which 21 were for T2 cancers. In 16 (76 percent) of the T2 patients, the tumors were completely removed with clear margins by transanal endoscopic microsurgery and no additional surgery was performed, except for 2 patients who developed radiation-induced complications. Radical surgery was performed in a second operation in five patients because of involved margins and residual disease was found in two. At a median follow-up of three years, all 12 patients who received local excision and radiotherapy remained disease free, whereas a 50 percent recurrence rate was observed in patients who refused adjuvant radiotherapy.ConclusionsThe results of this study support the feasibility of transanal endoscopic microsurgery for the treatment of selected patients with T2 rectal cancer. The addition of radiotherapy may decrease the rates of early local recurrence. However, at present, this treatment strategy should not be routinely considered for patients who may undergo radical procedures.

Is mechanical bowel preparation mandatory for left-sided colonicanastomosis? Results of a prospective randomized trial

AbstractBackgroundPreoperative mechanical bowelnpreparation is aimed to reduce the risk of infectious complications,nand its utility is a dogma in left-sided largenbowel anastomosis. The aim of this study was to specificallynassess whether colocolonic and colorectal anastomosesnmay be safely performed without preoperative mechanicalnbowel preparation.MethodsPatients undergoing electivencolon and rectal surgery with primary colocolonic or colorectalnanastomosis were prospectively randomized intontwo groups. The “prep” group had mechanical bowel preparationnprior to surgery, while the “non-prep” group hadnsurgery without pre-operative mechanical bowel preparation.ResultsTwo hundred forty-nine patients were includednin the study, 120 in the prep group and 129 in the nonprepngroup. Demographic characteristics, indications fornsurgery, and type of surgical procedure did not significantlyndiffer between the two groups. There was no difference innthe rate of surgical infectious complications between thentwo groups. Overall infectious complication rate was 12.5%nin the prep group and 13.2% in the non-prep group. Woundninfection, anastomotic leak, and intra-abdominal abscessnoccurred in 6.6%, 4.2%, and 1.6% of patients in the prepngroup and in 10.0%, 2.3%, and 0.7% of patients in the nonprepngroup, respectively (p=NS).ConclusionsThese resultsnsuggest that elective left-sided anastomosis may be safelynperformed without mechanical preparation. Multicenternstudies to test the reproducibility of these results arenrequired, to support a change in this time-honored practice.

Alterations in the Expression of the Cell Cycle Regulatory Protein Cyclin Kinase Subunit 1 in Colorectal Carcinoma

Low levels of p27Kip1 are associated with high aggressiveness and poor prognosis in various malignancies, including colorectal carcinoma. The authors showed that S phase kinase protein 2 (Skp2), the specific ubiquitin ligase subunit that targets p27Kip1 for degradation, was overexpressed and was inversely related to p27Kip1 levels in patients with colorectal carcinoma. The essential role of cyclin kinase subunit 1 (Cks1) in Skp2‐dependent p27 degradation was recently discovered, but its role in human malignancies is unknown.

The role of fine-needle aspiration and intraoperative frozen section in the surgical management of solitary thyroid nodules.

Abstract.Purpose: We evaluated the role of intraoperative frozen section (FS) in the surgical management of solitary thyroid nodules, as its true value is a subject of some controversy.nMethods: We reviewed the records of 206 consecutive patients operated on for solitary thyroid nodules. All patients had undergone both preoperative fine-needle aspiration (FNA) and intraoperative FS. The diagnostic findings of FNA cytology and FS histology were compared with the final histological results.nResults: There were 61 patients with cancer and 145 with various benign conditions. The sensitivity and specificity of FNA were 78.1% and 96.5%, respectively, demonstrating an overall accuracy of 91.3%. The sensitivity, specificity, and accuracy rates for FS were 83.3%, 95.2%, and 91.7%, respectively. FS altered the operative decision in 14 patients, but correctly so in only 8 patients. Correlated with FNA cytology, the yield of FS in assisting in the intraoperative decision making was 1.8%, 3.4%, and 5.2% for benign, malignant, and suspicious cytology, respectively.nConclusions: When the results of FNA and FS are interpreted as either benign or malignant, both are highly accurate predictors of the pathological nature of the nodule. However, the findings of the present study do not support the use of FS in the surgical management of solitary thyroid nodules, regardless of FNA cytology.