A pilot study assessing the efficacy of posterior tibial nerve stimulation in the treatment of low anterior resection syndrome.

BACKGROUND: Low anterior resection for rectal cancer often results in severe bowel dysfunction, specifically low anterior resection syndrome (LARS), with symptoms such as incontinence, urgency, and frequent bowel movements. Percutaneous tibial nerve stimulation (PTNS) resulted in a high rate of success in patients with fecal incontinence. The aim of this study was to evaluate the effectiveness of treatment with PTNS in LARS and to identify predictors of the outcome of the technique. METHODS: The study was conducted from May 2012 to April 2015 at the Alvaro Cunqueiro Hospital, University Hospital Complex of Vigo, Spain. Ten patients with LARS were recruited consecutively. All patients underwent 2 sessions per week (30 min each one) for 6 weeks. Patients were followed for 3 weeks, and those who had a significant clinical improvement were recruited to a second phase of PTNS. Some patients presenting with relapse during follow-up underwent an additional phase of PTNS. Outcome measures included Wexner scores, quality of life scores, and urgency of defecation. RESULTS: Three patients did not complete the treatment due to poor response in the first phase. Incontinence was reduced in the remaining seven of ten patients. The median Wexner score at initial patient evaluation was 14 (IQR 10.75-18.5), which decreased to 10 (IQR 6.5-18) after treatment (p = 0.034). A statistically significant improvement was demonstrated in quality of life scale, lifestyle, depression, and daily defecation urgency (p < 0.05). LARS Score improvement was observed in five patients (50%) with a total resolution of LARS in 2 (20%). CONCLUSIONS: PTNS is an ambulatory treatment that could play an important role in the context of a multimodal treatment approach in patients with LARS. It could be a first-line treatment to identify non-responders to conservative management who need different and more invasive treatments.

Osteoclast abnormalities in fractured bone during bisphosphonate treatment for osteoporosis: a case report.

Bisphosphonates have been widely used in the treatment of an array of bone disorders. Recent complications have included unusual femoral fractures in patients who have received long term bisphosphonate treatment for osteoporosis. Although it has been shown that bisphosphonates are effective by blunting osteoclast resorption, there has been little morphologic description of the local tissue activity at the site of these unusual fractures. To evaluate for local changes to bone morphology at the fracture site in patients presenting with a bisphosphonate-related femur fracture, a sample of cortical bone was obtained at the site of a bisphosphonate fracture and was processed in a nondecalcified manner. The specimen was evaluated for potential cellular changes consistent with bisphosphonate treatment. Significant osteoclast abnormalities at the fracture site were found in a 69-year-old woman treated for 2 years with Fosamax substantiating that bone remodeling at this site is distinctly abnormal. Addressing the osteoclast dysfunction should be a focus of future therapeutic attention and intervention.

Surgical issues after neoadjuvant treatment for gastric cancer.

Gastric carcinoma is one of the most frequent malignancies in the world and its clinical behavior depends on the metastatic potential of the tumour. Particularly, lymphatic metastasis is one of the main predictor of tumour recurrence and survival and current pathologic staging systems reflect the concept that lymphatic spread is the most relevant prognostic factor in patients resected with curative intent. This is deducted by the observation that two thirds of gastric cancers in the western world present at an advanced stage, with nearly 85% of tumors accompanied by lymph node metastasis at diagnosis. To date most therapeutic efforts are directed toward individualization of therapeutic protocols, tailoring the extent of resection integrated by the administration of preoperative and postoperative treatment. The goal of such strategies is to improve prognosis towards the achievement of a curative resection (R0-resection) with minimal morbidity and mortality, with better postoperative quality of life. A brief review of literature about preoperative therapy for gastric carcinoma will be herein illustrated. The rationale and the general drawbacks of preoperative treatments will be both discussed in order to demonstrate its value in terms of safety and efficacy.

Long-term outcomes in ypT0 rectal cancers: An international multi-centric investigation on behalf of Italian Society of Surgical Oncology Young Board (YSICO).

AIM: To investigate the outcome and pattern of survivals of rectal cancer patients presenting a complete or nearly complete tumor response after neo-adjuvant treatment. METHODS: Young surgeons <40 years old affiliated to the Italian Society of Surgical Oncology (YSICO) from 13 referral centers for colorectal cancer treatment, were invited to participate a retrospective study. Records from patients treated from 2005 to 2015 with a pathological diagnosis of ypT0/ypTis were retrieved and pooled in a common data-base for statistical purposes. All clinical and pathological variables were reviewed. Univariate and multivariate analyses were conducted with the end-point of survivals. RESULTS: Two hundreds and sixty-one patients were analyzed including 237 ypT0 and 24 ypTis. Nodal positive patients were 8.7%. More than sixty-six percent of the patients did not perform adjuvant chemotherapy, with a statistical difference comparing N0 versus N+ patients (66.8% vs 40.9%, p 0.02). Mean follow-up was of 47.6 months. Twenty-two relapses were observed, 91.6% at a distant site. The mean time to recurrence was of 35.3 months. On univariate analysis, the use of adjuvant chemotherapy correlated with better OS exclusively in ypT0N + patients and not in ypT0N0. Univariate and multivariate analyses documented nodal positivity as the only prognostic factor correlated with a worse OS. CONCLUSION: Recurrences were mostly diagnosed at a distant site and within the third year of follow-up. Nodal positivity was the only variable independently correlated with a worse OS. Univariate analysis documented a benefit for the use of adjuvant chemotherapy treatment exclusively in ypT0N + rectal cancers.

Response to neoadjuvant chemotherapy and effects of tumor regression in gastric cancer.

AIMS: Aim of this study is the evaluation of the effects induced by neoadjuvant chemotherapy (NACT) and its impact on survival on a series of locally advanced gastric carcinomas. METHODS: Downstaging was assessed comparing pre-treatment clinical and laparoscopic staging with post-operative pathologic staging on 30 consecutive patients who completed a 3-year follow-up. Tumor downstaging and the grade of pathologic response were included in a statistical correlation between tumor regression induced by NACT and 3-year survival. RESULTS: In this series tumor downstaging was obtained in 13 out of 30 patients. After the completion of 3-year follow-up, overall survival was >37.5months with an overall survival rate of 56.7%; this figure reached up to 70.8% in those cases who benefited from a R0-resection (24/30 patients: R0-resection rate 80.0%). CONCLUSIONS: In this study the 3-year survival for locally advanced gastric cancer treated by NACT prior to "D2" surgical resection, compares favourably with historical series treated by surgery alone. Patients who obtained T-downstaging and subsequently benefited from a R0-resection had a definitely better chance of cure, according to a complete 3-year follow-up.

Eosinophilic Metallosis: A Newly Described Entity in Failed Metal-on-Metal Arthroplasty.

In recent years, metal-on-metal (MoM) orthopaedic implants have been associated with significant adverse tissue reactions, prompting revision surgeries and recalls by manufacturers. Adverse tissue reactions consist of a wide range of pathologic findings but are generally characterized by a histiocytic reaction to metal debris, with or without an inflammatory response. Inflammation is generally that of a lymphocytic infiltration that prompts concern of an immune reaction. Only occasionally have eosinophils been documented-never as a marked infiltrate. In this article, we present the first histologic description of a dominant eosinophilic infiltrate associated with MoM arthroplasty. In our case report, the patient is a 53-year-old woman who presented with recurrent fluid collections surrounding the hip after a MoM total hip arthroplasty. At the time of surgical revision, tissue samples were taken and found to consist of lymphocytes and a prominent infiltrating eosinophilia. To our knowledge, no factors predictive of this type of tissue response have been identified, and its significance remains unclear despite ongoing research about the nature of the immune response to metal. Future work may help to elucidate whether the type and significance of this response can be predicted preoperatively and modulated, if necessary, postoperatively.

Bone disease in prolonged parenteral nutrition: osteopenia without mineralization defect.

A metabolic bone disease characterized by a mineralization defect, low plasma 1,25(OH)2D, and hypercalciuria has been described in patients receiving prolonged total parenteral nutrition (TPN). Because the practice of TPN differs from center to center, we investigated 13 home TPN patients to determine whether they had similar or different bone abnormalities. They had received TPN for a mean period of 51 +/- 38 mo. Bone pain occurred in six patients and two had multiple vertebral and rib fractures (with trauma in one patient). Bone pain was mild to moderate and not incapacitating. Bone histomorphometry showed reduced bone volume, reduced osteoid with normal resorption and calcification rates. These abnormalities were associated with hypercalciuria, but the plasma levels of 1,25(OH)2D were normal. Abnormalities in bone metabolism in this group of patients suggest a fundamental decrease in bone matrix-formation rather than a mineralization defect as the underlying mechanism.

Acidosis-induced osteomalacia: metabolic studies and skeletal histomorphometry.

The pathogenesis of osteomalacia was investigated in three patients with chronic metabolic acidosis. Serum levels of parathyroid hormone and vitamin D metabolites were measured, and bone biopsy specimens were analyzed after double tetracycline labeling. Parathyroid hormone concentrations were normal in patients 1 and 3 and slightly elevated in patient 2. Vitamin D metabolism was undisturbed. Static indicators of bone remodeling substantiated the diagnosis of osteomalacia in each case. In patient 1 fluorescent microscopy revealed no evidence of tetracycline uptake. In patients 2 and 3 active mineralization was evident at all osteoid seams, but because double labels were rare, the mineral apposition rate appears to have been substantially reduced in most bone-forming units. Our results indicate that acidosis-induced osteomalacia, unlike that due to vitamin D deficiency, may be associated with mineral deposition at every possible site. Nevertheless, like other causes of osteomalacia, metabolic acidosis prevents mineral apposition at a normal rate even if mineral deposition is ubiquitous. We suggest that titration of newly deposited phosphate causes the observed impairment of mineral apposition and ultimately leads to osteomalacia.

Histochemical demonstration of iron but not aluminum in a case of dialysis-associated osteomalacia.

A patient undergoing hemodialysis is described in whom osteomalacia developed despite protracted treatment with calcitriol. Appropriately stained biopsy sections exhibited iron at all marrow-osteoid interfaces and a small fraction of trabecular mineralization fronts. Aluminum, the metal usually associated with osteomalacia in patients undergoing hemodialysis, was not histochemically demonstrable, even though spectrophotometrically measured bone aluminum content was substantial. These observations suggest two interpretations: iron may have caused osteomalacia through effects on bone cells and at mineralization fronts; alternatively, aluminum may have caused osteomalacia while remaining histochemically undetectable. It is possible that both metals exerted toxic effects simultaneously.

The bone biopsy protocol for evaluating osteoporosis and osteomalacia.

Although this paper has dealt with well-established diagnostic procedures, I have attempted to present a practical summary based on experience with over 400 cases. A complete and modern approach to the evaluation of the bone biopsy for metabolic bone disease may be summarized as follows: Preoperative double labeling with tetracycline (two 3-day courses of tetracycline separated by 12 days); Full-thickness iliac bone biopsy yielding a 5- to 6-mm diameter specimen; Undecalcified sectioning (5-10 mu) processed in glycol or methyl methacrylate; Histomorphometric analysis with light microscope and planimeter; Tetracycline analysis with fluorescent microscope.

Microscopic bone pathology in two cases of surgically treated secondary hyperparathyroidism. Report of a distinct skeletal lesion.

We report bone biopsy findings in two hemodialysis patients with a history of secondary hyperparathyroidism treated by parathyroidectomy. Discrete, punched-out lesions in trabecular bone, which show little evidence of resorption or osteoblast activity, probably correspond to previous zones of osteoclastic tunneling resorption. Because we have seen these lesions in no other clinical setting, we suggest that they are residua of healed secondary hyperparathyroidism in dialysis patients. Their persistence may be due in part to aluminum intoxication.

Intracortical osteosarcoma.

A case of osteosarcoma arising in the tibia of a 15-year-old boy is reported. Of particular interest was the benign roentgenographic appearance and the confinement of the tumor within the cortex of the bone, an extremely rare phenomenon consistent with origin within the primitive mesenchyme of the Haversian canals.

Sampling error in diagnosing hyperparathyroid changes in bone in small needle biopsies.

Sampling error in diagnosing the effects of hyperparathyroidism on bone was studied retrospectively by subdividing large-core bone biopsy samples and evaluating them histologically. We used intratrabecular osteoclastic tunneling resorption as the diagnostic feature of secondary hyperparathyroidism in 10 hemodialysis patients. All biopsies were taken with a large-core bone biopsy instrument, resulting in a mean biopsy width of 5 mm. The processed tissue slides were divided into halves (mean width 2.5 mm) and subsequently into thirds (mean width 1.6 mm), mimicking smaller bone biopsy instruments such as the Jamshidi needle. In 30% of the cases the diagnosis of secondary hyperparathyroidism would have been missed if taken by a Jamshidi-type needle, and 60% if taken by a needle with a core diameter of 1.6 mm. Our findings emphasize the necessity of utilizing large-core bone biopsies in diagnosing certain metabolic bone diseases.

Absence of correlation between coronary arterial atherosclerosis and severity or duration of diabetes mellitus of adult onset.

The relation between the severity and duration of diabetes mellitus and the severity of ischemic heart disease is uncertain. The clinical findings and the findings at autopsy were studied in 185 patients with diabetes mellitus of adult onset who ranged in age from 37 to 91 years and had a clinical diagnosis of diabetes established for a few days to 50 years before death. No statistically significant association was demonstrated either by simple correlation or by multivariate regression analysis between the clinically diagnosed severity or duration of diabetes and either the overall coronary disease, the number of diseased vessels or the number of myocardial infarctions. The presence of other expected correlations in the multivariate analysis suggested that the results of this study were not spurious. However, comparison with 185 age- and sex-matched control patients revealed that on the average, diabetic patients have more overall coronary disease (p < 0.002), more diffuseness of coronary disease (p < 0.005), more coronary collateralization (p < 0.001), more vessels involved by atherosclerosis (p < 0.001) and more myocardial infarcts (p < 0.001). The results suggest that although diabetes mellitus of adult onset is a condition in which the larger coronary arteries are subject to more atherosclerosis than are those in nondiabetic subjects, the progression of the atherosclerotic disease is unrelated to the duration or severity of the diabetes mellitus.

Localization of osteoid osteomas--use of radionuclide scanning and autoimaging in identifying the nidus.

Surgical excision of osteoid osteomas is curative, but intraoperative localization and pathologic identification in submitted fragments may be difficult. We used preoperative technetium-99m methylene diphosphonate injection and intraoperative probing to localize the nidus of three clinically suspected cases of osteoid osteoma. Then in the pathology department, fine grain specimen x-rays and specimen autoimaging on undeveloped film were utilized. In all cases, technetium radioactivity localized within the lesion. Although the nidus was identified by fine grain specimen x-rays in only one case, the subsequent histologically proved osteoid osteoma corresponded in all cases to the fragment with the most intense autoimaging. We conclude that isotope scanning is effective in localizing osteoid osteomas at surgery, and autoimaging is effective in identifying the nidus itself by the pathologist.

Intramembranous localization of bacteria in beta-hemolytic group B streptococcal chorioamnionitis.

An unusual pathologic finding consisting of large colonies of bacteria, localized immediately beneath the epithelial layer of the amnion, has been observed in association with an example of group B beta-hemolytic streptococcal chorioamnionitis. Postpartum endometritis as well as neonatal sepsis and meningitis occurred. Histologic examination of the umbilical cord and placenta revealed routine features of intraamniotic inflammation, but the membranes were characterized by the presence of unusual darkly staining deposits of material immediately beneath the amniotic epithelium. Subsequent special stains revealed these to be colonies of gram-positive cocci. We have been unable to find a previous description of this observation in association with streptococcal or with other types of chorioamnionitis.

Squamous-cell carcinoma of Stensen's duct.

A case of epidermoid carcinoma of Stensen's duct, the major duct of the parotid gland, is reported, The literature on this rare tumor is reviewed including four previously reported cases. In the current case, both the gross appearance of the tumor confined to the duct and the lack of histologic involvement of adjacent parotid tissue establish that the carcinoma arose from the duct itself, presumably following development of squamous metaplasia. The patient was alive without evidence of disease 12 months following surgery.

Localization of technetium-99m methylene diphosphonate in bone using microautoradiography.

Technetium-99m methylene diphosphonate ([99mTc]MDP) is the most widely used bone-scanning agent today. In order to determine the precise bone locus of 99mTc corresponding to the delayed bone scan image, and to test the potential clinical use of this agent in enhancing the information obtained by bone scan, we employed [99mTc]MDP in this microautoradiographic study of normal bone and bone reparative tissue. Four white rabbits underwent operations in which two 1.5-mm drill holes were created in the subtrochanteric regions of both of their femora. An additional four white rabbits underwent sham operations of their femora, in which neither drilling nor periosteal injury occurred. Two rabbits were controls and did not undergo operation. After 7 days, the first two groups of rabbits were injected with [99mTc]MDP and bone scanned 2 h later. After the scans were completed, all three groups of animals were killed and their femora histologically processed for microautoradiography and routine histopathology. In the two groups that were injected with [99mTc]MDP, all bones showed the isotope to be clearly localized along mineralization fronts. The isotope was occasionally found in the substance of the osteoid, but was absent from the cytoplasm and nuclei of osteoblasts and osteocytes. Osteocytic lacunae showed the presence of isotope at their borders, but no identifiable pattern of isotope uptake was noted. Neither osteoclasts nor Howships lacunae showed isotope uptake.(ABSTRACT TRUNCATED AT 250 WORDS)