Israel Medical Association Journal

Background: Serum lactate dehydrogenase (LDH) is elevated in various diseases. 

Objectives: To analyze serum LDH as a distinguishing clinical biomarker and as a predictor of in-hospital outcome in admitted medical patients.

Methods: We analyzed a cohort of all 158 patients with very high isolated LDH (LDH ≥ 800 IU/ml – without concomitant elevations of alanine aminotransferase and aspartate aminotransferase) – admitted to our internal medicine department during a 3 year period. Epidemiologic and clinical data, as well as the final diagnosis and outcome were recorded and compared with those of a cohort of all 188 consecutive control patients.

Results: Very high isolated LDH was a distinguishing biomarker for the presence of cancer (27% vs. 4% in the LDH group and controls respectively, P < 0.0001), liver metastases (14% vs. 3%, P < 0.0001), hematologic malignancies (5% vs. 0%, P = 0.00019), and infection (57% vs. 28%, P < 0.0001). Very high isolated LDH was a marker for a severe prognosis, associated with more admission days (9.3 vs. 4.1, P < 0.0001), significantly more in-hospital major complications, and a high mortality rate (26.6% vs. 4.3%, P < 0.0001). Finally, very high isolated LDH was found in a multivariate regression analysis to be an independent predictor of mortality.

Conclusions: The presence of very high isolated LDH warrants thorough investigation for the presence of severe underlying disease, mostly metastatic cancer, hematologic malignancies and infection. Moreover, it is a marker for major in-hospital complications and is an independent predictor of mortality in admitted medical patients. 

Background: Atherosclerosis is a well-established inflammatory disease in which T helper 1 (Th1) cells play a key role. Regulatory T (Treg) cells drive a shift from Th1 to Th2 response and were shown to be reduced in atherosclerosis. ST2/interleukin (IL)-33 signal was found to promote Th2 response, attenuating atherosclerotic plaque progression.

Objectives: To evaluated the effect of IL-33 on Treg cell number.

Methods: We employed flow cytometry to determine Treg cell number, as well as ST2 levels, among splenocytes of C57BL/6J vs ApoE-/- mice. Soluble ST2 (sST2) levels were detected by enzyme-linked immunosorbent assay. 

Results: IL-33 contributed to an increase in Treg cells, but this association was attenuated in ApoE knockout (ApoE-/-) atherosclerotic mice. As a possible mechanism we demonstrated a reduction in the levels of CD4+ST2+ cells by flow cytometry, which is cotemporary to the previously described decrease in Treg cells in ApoE-/- mice. Additionally, the serum level of the soluble ST2 (sST2) decoy receptor was higher in ApoE-/- mice than in control animals.

Conclusions: Our results suggest that a repressed ST2/IL-33 signaling may contribute to the decrease in Treg cells observed in atherosclerosis.
 

Background: Gastric stump cancer is often described as a tumor with a poor prognosis and low resectability rates.

Objectives: To compare the pathological characteristics of gastric stump cancer patients with those of patients with proximal gastric cancer.

Methods: This retrospective study was based on the demographic and pathological data of patients diagnosed with gastric cancer and treated at Assaf Harofeh Medical Center during an 11 year period. The patients were divided into two groups: those undergoing proximal gastrectomy for proximal gastric cancer and those undergoing total gastrectomy for gastric stump cancer.

Results: Patients with gastric stump cancer were predominantly male, older (P = 0.202, not significant), and had a lower T stage with less signet-ring type histology, fewer harvested and fewer involved lymph nodes (P = 0.03, statistically significant) and less vascular/lymphatic involvement than patients with proximal gastric cancer.

Conclusions: The lower incidence of involved lymph nodes and lymphovascular invasion in gastric stump cancer as compared to proximal gastric cancer in this study may imply that the prognosis of gastric stump cancer may be better than that of proximal gastric cancer. However, to verify this assumption a study comparing patient survival is required.
 

Background: Gastric cancer continues to be a leading cause of cancer death. The treatment approach varies, and preoperative staging is therefore crucial since an exploratory laparotomy for unresectable gastric cancer will be followed by an unacceptably high morbidity and mortality rate.

Objectives: To assess the added value of diagnostic laparoscopy to conventional methods of diagnosis such as computed tomography in avoiding unnecessary laparotomies.

Methods: A retrospective study on 78 patients scheduled for curative gastrectomy based on CT staging was conducted. DL[1] was performed prior to exploratory laparotomy.

Results: In 23 of 78 patients (29.5%), unexpected peritoneal spread not detected on preoperative CT was found. Fifty-five patients underwent radical gastrectomy, 15 patients were referred for downstaging and 8 patients underwent a palliative procedure.

Conclusions: Based on our results, DL should be considered in all gastric cancer patients scheduled for curative gastrectomy.

Background: Infiltrating ductal carcinoma and infiltrating lobular carcinoma account for more than 90% of all invasive breast cancer histological types. The rate of ILC[1] is reported to be increasing steadily in the United States and Europe.

Objectives: To describe the trend in the incidence of ILC in a large cohort of patients who underwent surgery in a single institution over an 18 year period.

Methods: Our comprehensive database of 2175 consecutive patients with invasive breast cancer diagnosed during the period 1992–2009 served for the analysis. Several potential factors associated with lobular carcinoma as compared with ductal carcinoma were evaluated.

Results: During this period, a 2.4-fold increase in the incidence of pure ILC was noted, from 4.6% in the years 1992–1994 to 10.9% in 2004–2006, followed by a modest decrease to 8.7% in 2007–2009. A significant association of lobular malignancies with external hormonal use was noted, including hormone replacement therapy exposure in patients diagnosed at age 50–64, and ovarian overstimulation during in vitro fertilization in those diagnosed at age 50 or less.  

Conclusions: Better diagnostic tools – such as the liberal use of ultrasound and magnetic resonance imaging – and more accurate pathological definition for ILC type appear to influence the changes in the incidence of ILC in the subgroups of invasive breast cancer.

Background: One of the ominous complications following proximal gastrectomy or total gastrectomy is a leak from the esophagogastric or esophagojejunal anastomosis. An upper gastrointestinal swallow study is traditionally performed to confirm the anastomotic patency and lack of any leak before oral feeding can be initiated.

Objectives: To challenge the routine use of UGISs[1] following proximal or total gastrectomy in order to check the integrity of the gastroesophageal or jejunoesophageal anastomosis.

Methods: The charts of 99 patients who underwent PG[2] or TG[3]  for malignant pathology were retrospectively reviewed. UGISs were performed on day 6 following surgery using a water-soluble material.

Results: The UGISs were normal in 95 patients, with none displaying any complication related to the gastroesophageal or jejunoesophageal anastomosis. All four patients who experienced a leak from the anastomosis had an early stormy postoperative course.

Conclusions: Routine use of an UGIS to detect a leak following PG or TG is not justified. UGIS should be performed whenever signs of abdominal sepsis develop following this type or surgery.

Background: Hypocalcaemia following thyroid and parathyroid surgery is a well-recognized potential complication.

Objectives: To determine the utility of intraoperative quick parathormone assay in predicting severe hypocalcemia development following parathyroidectomy for a single-gland adenoma causing primary hyperparathyroidism.

Methods: A retrospective cohort study was performed. IO-QPTH[1] values were measured at time 0 (T0) before incision, and 10 (T10) and 30 minutes (T30) following excision of the hyperfunctioning gland. Percent decrease in IO-QPTH at 10 minutes (T10), maximum percent decrease of IO-QPTH value, and lowest actual IO-QPTH value obtained at surgery were used to determine any correlation with the development of postoperative hypocalcemia requiring treatment.

Results: Percent decrease in IO-QPTH at 10 minutes, maximum percent decrease in IO-QPTH and lowest IO-QPTH value did not correlate with the lowest postoperative calcium levels measured 18 hours after surgery (r = 0.017, P = 0.860 r = 0.018, P = 0.850 and r = 0.002, P = 0.985 respectively). For the purposes of our analysis, patients were subdivided into three groups. Group 1 comprised 68 patients with normal calcium levels (serum Ca 8.6¨C10.3 mg/dl) Group 2 had 28 patients with hypocalcemia (8.1¨C8.6 mg/dl) Group 3 included 12 patients with severe hypocalcemia (calcium level ¡Ü 8.0 mg/dl) requiring calcium supplementation due to symptoms of hypocalcemia. There was no difference between the three groups in the lowest IO-QPTH value (P = 0.378), percent decrease in IO-QPTH (P = 0.305) and maximum percent decrease in IO-QPTH (P = 0.142).

Conclusions: IO-QPTH evaluation was not useful in predicting the group of patients susceptible to develop severe postoperative hypocalcemia.  

[1] IO-QPTH = intraoperative quick parathormone

Background: Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the human gastrointestinal tract.

Objectives: To review our accumulated experience using surgery to treat gastrointestinal stromal tumors.

Methods: We reviewed all patient charts and histological diagnoses of leiomyomas, leiomyosarcomas, leiomyoblastomas and schwannomas. Only tumors that displayed c-kit (CD117) immunopositivity were defined as GISTs[1].

Results: The study group comprised 40 female and 53 male patients (age 26–89 years); 40.9% of the tumors were classified as malignant, 39.8% as benign, and 19.4% as of uncertain malignancy. Fifty-six GISTs were located in the stomach (60.2%), 29 in the small bowel (31.2%), 4 in the duodenum (4.3%), 2 in the colon (2.1%) and 2 in the rectum (2.1%). Incidental GISTs were found in 23.7% of our patients. Mean overall survival time for malignant gastric GISTs was 102.6 months (95% confidence interval 74.2–131.1) as compared to 61.4 months mean overall survival for malignant small bowel GISTs (95% CI[2] 35.7–87) (P = 0.262). The mean disease-free survival period for patients with malignant gastric GISTs was 97.5 months (95% CI 69.7–125.2) as compared to only 49.6 months (95% CI 27.4–71.7) for patients with small bowel malignant GISTs (P = 0.041).

Conclusions: We found a high percentage of incidental GISTs. Gastric GISTs are more common than small bowel GISTs. Patients with malignant gastric GISTs have a significantly better prognosis than patients with malignant small bowel GISTs. A statistically significant correlation was found between age and malignant potential of the GIST.

Background: Sentinel lymph node mapping is the standard of care for patients with malignant melanoma and breast cancer. Recently, SLN[1] mapping was introduced to the field of gastric cancer.

Objectives: To evaluate SLN mapping in patients with gastric cancer.

Methods: In 43 patients with gastric cancer, open intraoperative subserosal dye injection in four opposing peritumoral points was used. Ten minutes following dye injection, stained LNs were located, marked and examined postoperatively from the surgical specimen.

Results: SLN mapping was performed in 43 with gastric cancer; 782 lymph nodes were harvested and evaluated. SLNs were stained in 34 of the patients (79.1%) with a mean of 2.85 SLNs per patient. The false negative rate was 20.9%, the positive predictive value 100%, the negative predictive value 78.6% and the sensitivity 86.9%.

Conclusions: SLN mapping in patients with gastric cancer is feasible and easy to perform. SLN mapping may mainly affect the extent of lymph node dissection, and to a lesser degree gastric resection. However, more data are needed.

Background: Among the various new technologies in the field of parathyroid surgery are intraoperative quick parathormone measurements.

Objectives: To evaluate the contribution of QPTH[1] measurements during parathyroidectomy to the achievement of higher success rates. 

Methods: QPTH assay using Immulite Turbo Intact PTH[2] was measured in 32 patients undergoing parathyroidectomy: 30 for primary and 2 for secondary hyperparathyroidism.  QPTH levels were measured at time 0 minutes (before incision) and at 10, 20, and 30 minutes after excision of the hyperfunctioning gland.  Only a drop of 60% or more from the 0’ level was considered to be a positive result.

Results: The mean QPTH level at time 0’ for PHPT[3] patients was 38.12 ± 25.15 pmol/L (range 9.1–118 pmol/L).  At 10 minutes post-excision of the hyperfunctioning gland (or glands), QPTH dropped by a mean of 73.80% to 9.89 ± 18.78 pmol/L. 

Conclusions: Intraoperative QPTH level measurement is helpful in parathyroid surgery.  A drop of 60% or more from 0’ level indicates a successful procedure, and further exploration should be avoided.