Presence of cancer cells in gastric lavage of gastric cancer patients as an indicator of advanced disease, predictor of tumour aggressive phenotype and independent prognostic factor for poor survival: The endoluminal metastatic pathway of gastric cancer and GL0/GL1 classification.

OBJECTIVE: As of 2017, the pathobiology of gastric cancer (GC) is far from fully understood; consequently, new methods of basic and advanced research have been proposed and tested. The presence (GL1) vs absence (GL0) of malignant cells exfoliated in gastric lavage (GL) of GC patients was formerly evaluated with diagnostic intent but not for staging or prognostic assessment. We investigated this hitherto unreported application of cytopathology. METHODS: GL was preoperatively and prospectively collected from 80 GC patients and cytologically analysed. The results were compared with the classic clinicopathological features of GC and related to survival. The prognostic value of GL1 was assessed through univariate and multivariate analyses. RESULTS: GL1 was detected in 36 samples (45%) and correlated with advanced tumour depth (T3-T4), lymphatic metastasis (N+), distant metastasis (M1) and lymphovascular invasion (LVI1; P=.0317, .0024, .003 and .0028, respectively). Overall survival (OS) was significantly shorter for GL1 (23 months) vs GL0 patients (42 months; P=.005) and GL1 vs GL0 T1 subjects (12.6 vs 47.8 months, P=.0029). Univariate analysis revealed that GL1, N+, M1, LVI1 and advanced stage were significantly associated with OS. Multivariate analysis assessed GL1 as the only independent prognostic factor for worse OS and progression-free survival (P=.0013 and .0107). CONCLUSIONS: In the present study, GL1 was correlated with advanced disease, aggressive tumour behaviour and poor prognosis. Although additional studies are needed to confirm these findings, the GL0/GL1 classification can be applied to GC patients to achieve higher accuracy in staging, prognostic stratification and treatment selection.

Procalcitonin, as an early biomarker of colorectal anastomotic leak, facilitates enhanced recovery after surgery.

PURPOSE: Procalcitonin (PCT) is a biomarker used to help sepsis diagnosing and monitoring and guide antibiotic therapy. Anastomotic leak (AL) after colorectal surgery is a severe complication associated with relevant short- and long-term sequelae. The aim of our study is to assess the predictive value of PCT levels to early diagnose AL after colorectal surgery. METHODS: Between September 2011 and September 2012, a series of 99 patients underwent colorectal surgery in our institution. In all cases, white blood cell (WBC) count, C-reactive protein (CRP), and PCT levels were measured in first, third, and fifth postoperative day (POD). Anastomotic leaks and all other postoperative complications were recorded. RESULTS: We registered 7 ALs (7.1%). Decreased PCT levels had a significant negative predictive value (NPV) for AL in third and fifth POD (96.7% and 96.7%, respectively), compared with CRP and WBC. The best diagnostic performance was obtained with the combination of PCT and CRP measurements in third and fifth POD (area under the curve, 0.87 and 0.94, respectively). In 5th POD, PCT improves diagnosis, but not in a statistically significant way (area under the curve, 0.86). CONCLUSIONS: Compared with more established biochemical values such as CRP and WBC, PCT is an earlier, more sensitive, and reliable marker of AL. Increased PCT levels in early PODs after colorectal surgery may provide a more effective way to detect AL, before clinical symptoms appear. Moreover, normal PCT values might be also a useful marker to facilitate a safe and early discharge of selected patients after colorectal surgery.

Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers.

BRAF(V600E) is the most frequent genetic mutation in papillary thyroid cancer (PTC) and has been reported as an independent predictor of poor prognosis of these patients. Current guidelines do not recommend the use of BRAF(V600E) mutational analysis on cytologic specimens from fine needle aspiration due to several reasons. Recently, immunohistochemistry using VE1, a mouse anti-human BRAF(V600E) antibody, has been reported as a highly reliable technique in detecting BRAF-mutated thyroid and nonthyroid cancers. The aim of this study was to test the reliability of VE1 immunohistochemistry on microhistologic samples from core needle biopsy (CNB) in identifying BRAF-mutated PTC. A series of 30 nodules (size ranging from 7 to 22 mm) from 30 patients who underwent surgery following CNB were included in the study. All these lesions had had inconclusive cytology. In all cases, both VE1 and BRAF(V600E) genotypes were evaluated. After surgery, final histology demonstrated 21 cancers and 9 benign lesions. CNB correctly diagnosed 20/20 PTC and 5/5 adenomatous nodules. One follicular thyroid cancer and 4 benign lesions were assessed at CNB as uncertain follicular neoplasm. VE1 immunohistochemistry revealed 8 mutated PTC and 22 negative cases. A 100% agreement was found when positive and negative VE1 results were compared with BRAF mutational status. These data are the first demonstration that VE1 immunohistochemistry performed on thyroid CNB samples perfectly matches with genetic analysis of BRAF status. Thus, VE1 antibody can be used on thyroid microhistologic specimens to detect BRAF(V600E)-mutated PTC before surgery.

Medullary thyroid nodules by measurement of calcitonin (Ct) in aspiration needle washout in patients with multinodular goiter and moderately elevated serum Ct.

The accuracy of fine needle aspiration cytology (FNAC) is low in medullary thyroid carcinomas (MTC). Recently, a few papers analyzed the measurement of calcitonin (Ct) in washout of the needle after aspiration (WO-Ct) suggesting that this approach may be useful in patients with high serum Ct. Here we reported, for the first time in our best knowledge, 3 patients with multinodular goiter, moderately elevated serum Ct, high value of WO-Ct, and medullary outcome. These findings suggest that in presence of high serum Ct, FNAC should be performed in all nodules, and it should be combined with WO-Ct in all cases.

Measuring calcitonin in washout of the needle in patients undergoing fine needle aspiration with suspicious medullary thyroid cancer.

Calcitonin measurement in washout of the needle after aspiration (WO-Ct) has been rarely evaluated. Here we analyzed the role of WO-Ct in a series of subjects who underwent fine needle aspiration (FNA) with suspicious medullary thyroid cancer (MTC). Twenty-one patients referred following elevated serum calcitonin (S-Ct) or suspicious MTC by cytology. All patients underwent re-evaluation of S-Ct, FNA, and measurement of WO-Ct. S-Ct and WO-Ct were assessed by chemiluminescence assay (IMMULITE 2000, Diagnostic Products Corporation, USA). S-Ct showed elevated value in six subjects (mean 368.8 ± 373.9 pg/ml), of which three cases were cytologically classified as Class 5. WO-Ct obtained in this group (304.0 ± 309.3 pg/ml) was no different from S-Ct. After surgery MTC was confirmed in all patients. In the other 15 patients MTC was excluded by cytology or histology. Two subjects had moderately skewed S-Ct with nonmedullary histology. In the remaining 13 patients S-Ct resulted normal (6.2 ± 5.6 pg/ml) and WO-Ct low (2.9 ± 2.2 pg/ml). Significant (two-tailed P < 0.05, r(2) = 0.27, 95% confidence interval = 0.017-0.81) correlation was found between S-Ct and WO-Ct in nonmedullary patients but not in MTC patients. This study showed that WO-Ct can play a role in diagnosing primary and metastatic MTC. The procedure is easy, cost effective, and should be used in patients undergoing FNA with elevated S-Ct. Further studies and guidelines for the method are needed to use this technique in clinical routine. Until this any institute should use itself cut-off.

[Pancreatic carcinoma presenting with invasion of the vena porta or the superior mesenteric vein: our experience and review of the literature]. / Carcinoma del pancreas con infiltrazione della vena porta o della vena mesenterica superiore: nostra esperienza e revisione della letteratura.

AIM: Adenocarcinoma of the pancreas can present with invasion of the vena porta or the superior mesenteric vein (SMV). Pancreatectomy with resection of the vena porta and/or the SMV remains controversial although the procedure is potentially curative. The aim of this study was to validate the indication for resection on the basis of our experience and evidence from recently published studies. METHODS: Studies published in the last 10 years on pancreatectomy (duodenocephalopancreatectomy, total and distal pancreatectomy) with resection of the vena porta and/or the SMV were retrieved from the Medline database and reviewed. A total of 18 studies meeting the inclusion criteria were analyzed for information about indications, type of intervention, use of adjuvant therapies, histopathology, perioperative results and survival in 620 patients with adenocarcinoma of the pancreas undergoing pancreatectomy with resection of the vena porta and the SMV. This data set was then compared with our experience with this procedure from the last 3 years. RESULTS: The mortality and postoperative complication rates varied between 0% and 7.7% and 12.5% and 54%, respectively. The median survival varied from 12 to 22 months; the 1 year survival rate was between 31% and 83%; the 5-year survival rate was between 9 and 18% according to the studies reviewed. CONCLUSION: On the basis of evidence from the literature and our experience, en bloc resection of the vena porta and/or the SMV during pancreatectomy appears to be a safe procedure with acceptable outcomes, and should be considered in patients with pancreatic cancer presenting with venous invasion. Venous resection increases the surgical cure rate, prolonging survival in patients selected according to correct indications.

Does normal thyroid gland by ultrasonography match with normal serum thyroid hormones and negative thyroid antibodies?

Few papers have shown that a hypoechoic appearance of the thyroid gland at ultrasonography (US) is related to a hypofunction and serum positivity of thyroid antibodies (T-Ab). However, it is not ascertained if normal thyroid appearance at US correspond to normal thyroid laboratory tests. The aim of this study was to assess the value of normal thyroid at US in predicting normal thyroid hormones and negative T-Ab in a cohort of 48 adult patients. All patients (37 females and 11 males) were referred to our hospital to undergo their first thyroid US examination, followed by a thyroid function evaluation. All subjects had normal thyroid gland at US. As a control group 65 patients with hypoechoic and inhomogeneous thyroid gland were enrolled. All 48 patients had normal free-T (3) and free-T (4) levels. While 41 patients (85.4%) showed normal TSH, in 7 subjects (14.6%) TSH was elevated and a significant (p < 0.001) difference was recorded between the two groups in mean TSH value. Positive T-Ab value was found in 5 patients (10.4%) and the remaining 43 patients (89.6%) had negative T-Ab. TSH was not significantly correlated with age, thyroid volume or BMI. The multivariate model showed that only BMI was significantly correlated to thyroid volume (p < 0.01, r(2)=0.31). These results showed that normal thyroid recorded by US matches with normal thyroid laboratory assessment to a large degree. These preliminary data need to be confirmed in a prospective study and in a larger series and should suggest the evaluation of thyrotropin and thyroid antibodies in subjects with normal thyroid gland as assessed by US.

[Teaching in the operative room: the benefit of daysurgery on surgical trainees]. / Attività didattica in sala operatoria: utilità della day-surgery nell'iter formativo dello specializzando in chirurgia.

AIM: Aim of the study was to evaluate the operative time and the incidence of post-operative complications in a group of patients undergoing Lichtenstein inguinal hernia repair performed either by surgical residents or senior surgeons in a day-surgery setting. PATIENTS AND METHODS: The study population consisted of 198 patients: group I (n=102), in which the operator was a senior surgeon, group II (n=96), in which the operator was a resident supervised by a senior surgeon. We recorded the duration of the operation and the complications following the procedure, and statistically compared them between group I and II. RESULTS: Our analysis showed that there was a statistically significant difference between the two groups only for the mean operative time, being shorter in group I (62 vs 82 min, p>0.05), while no significant difference was found for the incidence of complications. CONCLUSION: In conclusion, the day-surgery setting allows a high quality training of young surgeons, based on performing minor surgical procedures such has inguinal hernia repair. This training allows a step by step supervised learning process that does not jeopardize the efficacy of the treatment as well as the patient safety. The major cost due to the increase in operative time should be considered as an investment in young surgeons education.

[A rare presentation of Amyand's hernia. Case report and review of the literature]. / Un raro caso di ernia di Amyand.

Amyand's hernia is defined as an inguinal hernia within the hernial sac containing the appendix. It is a rare disease, reported in 1% of cases of inguinal hernia repair. The appendix can be complicated by acute appendicitis in 0.13% of cases. This disease is often very difficult to diagnose, and most of the time it can be confused with an incarcerated or strangulated inguinal hernia. Often, it requires an emergent surgical treatment. This article describes the case of a 82-year-old female who was admitted for an intestinal obstruction and a bulge in the right inguinal region. An abdominal computed tomography scan showed dilated small bowel loops with multiple air/liquid levels and one loop herniating into the right inguinal canal. The patient underwent a laparotomy that showed the presence of an acute appendicitis and a necrotized ileal loop protruding into the right inguinal canal. The patient underwent an appendectomy and small bowel resection and she was discharged on postoperative day 10. Amyand's hernia can be a challenge for the surgeon. Its treatment depends on the grade of inflammation of the appendix. In fact, it can range from the simple repair of the abdominal defect with a prosthetic mesh, to appendectomy, small bowel resection and repair of the abdominal wall defect without a mesh.

[Hepatic resections for hepatocarcinoma in the XXI century]. / Le resezioni epatiche per epatocarcinoma nel XXI secolo.

Hepatic resection is today the treatment of choice for cirrhotic patients affected by hepatocellular carcinoma (HCC). Short term results are now definitely satisfactory, with a mortality rate in the referral centers lower than 5%. However, long term results are affected by a high recurrence rate, between 50% and 100%, due to the underlying cirrhosis. Notwithstanding the high recurrence rate, the hepatic resection guarantees a five years survival between 40% and 60%, comparable to the one offered by liver transplantation. The aim of this paper is to review the results of studies on resected cirrhotic patients affected by HCC.

[Photodynamic therapy in cardiac and vascular surgery]. / Terapia fotodinamica in chirurgia cardiaca e vascolare.

One of the major drawbacks to therapeutic cardiovascular intervention is intimal hyperplasia and constrictive remodeling, which result in vascular restenosis. Neointimal hyperplasia is characterized by proliferation and migration of smooth muscle cells. These cells also produce new extracellular matrix, leading to narrowing of vessels. Photodynamic therapy (PDT) represents one of the most promising approaches to the inhibition of intimal hyperplasia. PDT requires the interaction among 3 factors: a source of light, usually a laser, a photosensitizer and oxygen. When the inert photosensitizer absorbs light of a specific wavelength, it is activated to an excited triplet state, generating reactive oxygen species. These free radicals are able to induce apoptosis of the smooth muscle cells that had absorbed the photosensitizer; they also induce changes in the extracellular matrix, reducing cell migration. Because of continued success of PDT in inhibiting intimal hyperplasia in experimental animal models, it is now being tested in clinical trials for vascular diseases. PDT offers many advantages to the surgeon since it can act on numerous factors responsible for vascular lesions. In the future PDT could be used in helping to overcome the inherent failures associated to vascular reconstruction. This treatment modality is emerging as an encouraging therapeutic option, either alone or as an adjunct to conventional treatment. However, more detailed clinical investigation are necessary to determine its full potential.

Papillary muscles and tendinous cords of the right ventricle of the human heart: morphological characteristics.

A series of 79 normal human hearts was studied focusing on the morphological characteristics of the papillary muscles of the right ventricle and their tendinous cords (chordae tendineae). The number, incidence, length and shape of the anterior, septal and posterior papillary muscles were observed. The tendinous cords attached to each papillary muscle were counted at their origin. The papillary muscles and the tendinous cords were measured in situ and after the removal of the right atrioventricular valve (tricuspid valve). The anterior and posterior papillary muscles (apm, ppm) were present in 100% of the cases. The septal papillary muscle (spm) was absent in 21.5% of the hearts. The apm presented 1 head in 81% and 2 heads in 19%; it was 19.16 mm in length. The spm was one-headed in 41.7% and presented two heads in 16.5%; the presence of a 3 and 4 heads appeared in 12.7% and 7.6% respectively; the spm was 5.59 mm in length. The ppm had 1 head in 25.4%, 2 heads in 46.8%, 3 heads in 21.5% and 4 heads in 6.3% of the cases; it was 11.53 mm in length. Tendinous cords (TC) varied as follows: from 1 to 11 TC originated in the apm (mean 4.74); from 1 to 8 TC originated in the ppm (mean 2.67) and from 1 to 5 TC originated in the spm (mean 1.77).

Laser-induced shock waves enhance sterilization of infected vascular prosthetic grafts.

BACKGROUND AND OBJECTIVE: Bacteria that cause infection of vascular prosthetic grafts produce an exopolysaccharide matrix known as biofilm. Growth in biofilms protects the bacteria from leukocytes, antibodies and antimicrobial drugs. Laser-generated shock waves (SW) can disrupt biofilms and increase drug penetration. This study investigates the possibility of increasing antibiotic delivery and sterilization of vascular prosthetic graft. STUDY DESIGN/MATERIALS AND METHODS: Strains of Staphylococcus epidermidis and S. aureus were isolated from infected prosthetic grafts obtained directly from patients. Dacron grafts were inoculated with the isolated bacteria, which were allowed to form adherent bacterial colonies. The colonized grafts underwent the following treatments: (a) antibiotic (vancomycin) alone; (b) antibiotic and SW (c) saline only; and (d) saline and SW. Six hours after treatment, the grafts were sonicated, the effluent was cultured and the colony forming units (CFU) were counted. RESULTS: CFU recovered from control grafts colonized by S. epidermidis were comparable: saline, 3.05 x 10(8) and saline+SW 3.31 x 10(8). The number of S. epidermidis CFU diminished to 7.61 x 10(6) after antibiotic treatment but the combined antibiotic+SW treatment synergistically decreased CFU number to 1.27 x 10(4) (P<0.001). S. aureus showed a higher susceptibility to the antibiotic: 2.26 x 10(6) CFU; antibiotic +SW treatment also had an incremental effect: 8.27 x 10(4) CFU (P<0.001). CONCLUSIONS: This study demonstrates that laser-generated shock waves have no effects alone, but can enhance the effectiveness of antibiotics against bacteria associated with prosthetic vascular graft biofilms, suggesting that this treatment may be of value as adjunctive therapy for prosthetic graft infections.

Photodynamic therapy induces apoptosis in intimal hyperplastic arteries.

Photodynamic therapy (PDT) generates free radicals through the absorption of light by photosensitizers. PDT shows promise in the treatment of intimal hyperplasia, which contributes to restenosis, by completely eradicating cells in the vessel wall. This study investigates the mechanisms of PDT-induced cell death. PDT, using the photosensitizer chloroaluminum-sulfonated phthalocyanine (1 mg/kg) and laser light (lambda = 675 nm) 100 J/cm(2) was administered to rat carotid arteries after balloon injury-induced intimal hyperplasia. Apoptosis was determined by cell morphology with light microscopy and transmission electron microscopy, DNA cleavage by terminal dUTP nick-end labeling staining, and nucleosomal fragmentation (ladder pattern) by DNA agarose gel electrophoresis. Four hours after PDT, apoptosis was observed in vascular cells, as evidenced by terminal dUTP nick-end labeling staining and transmission electron microscopy. Within 24 hours no cells were present in the neointima and media. Immunofluorescence using an alpha-smooth muscle cell actin antibody confirmed the disappearance of all neointimal and medial cells within 24 hours. No inflammatory cell infiltrate was observed during this time frame. Apoptosis was sharply confined to the PDT treatment field. These data demonstrate that vascular PDT induces apoptosis as a mechanism of rapid, complete, and precise cell eradication in the artery wall. These findings and the lack of inflammatory reaction provide the basis for understanding and developing PDT for a successful clinical application in the treatment of hyperplastic conditions such as restenosis.

[The use of autotransfusion in general surgery]. / L'uso dell'autotrasfusione in chirurgia generale.

Authors expose their experience with autotransfusion, made during several years in a general surgery university department. Discussion is made about ethic and economical aspect of the philosophy guiding the most general concept of blood sparing, and different methods of autotransfusion; attention is then focused on practical experience made during two years (1995-1997) when the program worked well. On the whole, in 94 patients, 172 blood units were collected plus 10 plasma units obtained by aferesis. No method-related complications are have been observed. Elements who corresponded to difficulties or obstacles to the fully application of the method have been critically analyzed. Authors propose finally guide-lines which want to be valid proposal to increase method use while respecting at the best ethics, economics, efficacy and efficiency that must guide our work.

Restorative proctocolectomy: histological assessment and cytometric DNA analysis of ileal pouch biopsies.

BACKGROUND/AIMS: The pathological changes and the risk of developing cancer in the ileal pouch mucosa of patients who received restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) were studied. The presence or absence of remaining rectal mucosa below the IPAA in both patients with stapled and handsewn IPAA was also examined. MATERIALS AND METHODS: Endoscopy of the ileal pouch was performed on 38 patients at 4, 12, 18 and 36 months after restorative proctocolectomy with ileal pouch. Mucosal biopsy specimens were taken from the ileal reservoir in order to assess the histological incidence of inflammation. In 23 patients, biopsies were taken to perform cytometric DNA analysis. Clinical symptoms of pouchitis (over six evacuations in 24 hours, night-time evacuations, leakage of feces, bloody diarrhea, abdominal pain and fever) were recorded and correlated with the histological findings. Biopsies were also sampled below the ileo-anal anastomosis (IPAA) in order to identify residual rectal mucosa. RESULTS: Results of histological assessment showed various degrees of chronic inflammation increasing over time (from 42 to 60%) while the presence of both acute and chronic inflammation of the reservoir was less frequent (from 18 to 30%). Villous atrophy was present in 39-68% of patients and the grade of villous atrophy was correlated to the grade of inflammation. Clinical pouchitis was present in 3 to 8% of cases at the different controls and it was always associated with the highest grade of histological inflammation and severe villous atrophy. No significant alteration of the DNA cellular content was observed. Very low incidence of aneuploidy (0.7-1% Ex.R.) has been reported in three cases. However, we found dysplasia in only one patient who underwent surgical treatment for familial polyposis coli. IPAA evaluation showed no residual rectal mucosa in 40% of cases with stapled IPAA; in the remaining 60%, we found a small amount of rectal mucosa (maximum 1 cm). We did not find rectal mucosa after handsewn IPAA with mucosectomy. CONCLUSIONS: Patients treated with restorative proctocolectomy with IPAA showed a higher and increased incidence of inflammation during follow-up. No significant alteration of DNA cellular content nor dysplasia of the pouch mucosa were observed. In this study the chance of leaving rectal mucosa after stapled IPAA was about 60%.

In-vitro effects of cardioplegic solutions on human saphenous vein endothelium--a scanning electron microscopy study.

In order to evaluate the effects of potassium cristalloid cardioplegic solutions (CPS) on the endothelial morphology, human saphenous veins were studied by scanning electron microscopy after exposure to three CPS named MKP (magnesium-potassium-procaine cardioplegia), LK (low-potassium cardioplegia), and HKA (high-potassium-albumin cardioplegia) and to their main components. Vein rings, selected from the saphenous veins sampled for graft harvesting in 63 patients undergoing aorto-coronary bypass surgery, were exposed for 30, 60, and 120 minutes to the following buffered solutions: Krebs bicarbonate (as control); MKP cardioplegia; KCl (16.0 mmol/L); MgCl2(2).6H2O (16.0 mmol/L); Procaine (0.05 mmol/L); NaCl (92.5 mmol/L); LK cardioplegia; KCl (10.0 mmol/L); Mannitol (74.3 mmol/L); Glucose (27.7 mmol/L); HKA cardioplegia; KCl (30 mmol/L). Severe endothelial lesions, consisting of diffuse disendothelialization and diffuse signs of endothelial suffering, were induced by KCl (30 and 16 mmol/L) after 60-120 min, and by MKP cardioplegia and KCl (10 mmol/L) after 120 min. Moderate endothelial lesions, characterised by diffuse endothelial surface changes and focal cellular loss, were induced by KCl (30 and 16 mmol/L) after 30 min, MKP cardioplegia and KCl (10 mmol) 30-60 min, LK cardioplegia, HKA cardioplegia, and MgCl2.6H2O after 120 min. Slight endothelial lesions, consisting of diffuse endothelial bulging, or absence of significant endothelial changes, were found in samples otherwise treated. Our findings showed a significant damaging effect of CPS on the human saphenous vein endothelium in-vitro. The endothelial lesions seemed related to the presence of potassium and magnesium, and to prolongation of the time of exposure to the cardioplegic solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Subcellular structure of the atrial myocardium of children in cases of atrial septal defect.

In order to study the initial development of myocardial ultrastructural changes owing to right atrium volume overload, myocytes have been studied in specimens taken from the right atrial wall and auricle of four children aged 1 to 6 years with ostium secundum atrial septal defect undergoing cardiac surgery. The younger patients (1 to 4-year-old children) we observed did not show diffuse and significant myocardial ultrastructural damages. The most significant myocardial changes were observed in the 2 older patients (six years old) as we found subcellular signs of myocardial hypertrophy such as an increased number of mitochondria, increased glycogen inclusions, areas of new sarcomerogenesis and nuclei lobulated and variably shaped. Focal degenerative changes, such as rupture of mitochondrial cristae and intercellular fibrosis were also noted. These changes may be considered as the initial features of myocardial hypertrophy because they were not as severe and diffuse as those usually seen in a marked functional failure.