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.

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.

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.

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.

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.

Gorham's disease: an autopsy report.

We present the case report of a 35-year-old man with Gorham's disease (disappearing bone disease, massive osteolysis) with initial clinical findings of small bowel lymphangiomatosis and multicentric osteolysis. The patient, who otherwise was healthy, had a chylothorax develop and he died 9 months later of thoracic and pulmonary complications. An autopsy revealed absence of the proximal thoracic duct and significant lymphangiectatic abnormalities of the pleural, peritoneal, diaphragmatic, splenic, and small bowel tissue with lymphangiomatous masses in the thoracic and mediastinal regions. The findings suggest a subtype of Gorham's disease characterized by a dysplastic lymphatic system. Osteolysis was correlated anatomically with lymphangiectatic tissue, suggesting mediation of osteoclastic resorption via local lymphatic tissue factors.

[Clinical significance and prognostic value of tumor maximum diameter in gastric carcinoma]. / Significatività clinica e valore prognostico del diametro massimo del tumore nel carcinoma gastrico.

Maximum tumor diameter (MTD) is considered by many authors as an important prognostic factor in gastric cancer and, in some series, is reported to be strongly correlated with depth of infiltration. Aim of this study was to evaluate the prognostic value of tumor diameter in a monoistitutional series of 153 gastric cancer patients. The Spearman correlation coefficient was also calculated between MTD and other known prognostic factors. For statistical analysis, patients were grouped as follows: MTD 1, < or = 40 mm, and MTD2, > 40 mm. In our series, MTD resulted significantly linked to survival at univariate analysis (p = 0.0001), but multivariate analysis did not evidence MTD as an independent prognostic indicator. The Spearman correlation test documented that MTD2 is strongly correlated with tumor depth (pT), nodal status (pN) and p-stage (p < 0.01) and is a good predictor of locally advanced stage. This retrospective study showed that patients with larger tumor are at an increased risk for tumor advancement and, therefore, MTD could represent a useful parameter for choosing the most appropriate therapeutic strategy.

[Ratio of lymph node metastasis in gastric carcinoma after D2 gastrectomy]. / La ratio dei linfonodi metastatici nel carcinoma gastrico dopo gastrectomia D2.

The classification of lymph node metastasis in patients with gastric carcinoma is controversial. In the past, all systems used for this disease defined N classification by the location of lymph node metastases relatively to the primary tumor. In the 1997, the UICC and AJCC redefined the pathologic nodal status on the basis of the number of involved nodes rather than their location. More recently, the ratio between the number of metastatic and the total examined lymph nodes has been proposed as a new quantitative staging system. Aim of our study was to clarify the outcome of the ratio of the metastatic lymph nodes (RML) in a monoinstitutional series of 164 patient with primary gastric cancer who underwent gastrectomy with D2 lymph node dissection. Our data showed that ratio of metastatic lymph nodes is a simple, convenient, and reproducible staging system with an ability to predict surgical results and it is an independent prognostic factor after D2-gastrectomy.

[T-downstaging after neoadjuvant chemotherapy in locally advanced gastric carcinoma]. / T-downstaging dopo chemioterapia neoadiuvante nel carcinoma gastrico localmente avanzato.

Only a limited number of trials on neoadjuvant chemotherapy for resectable advanced gastric cancer have been planned or conducted up to date, still in recent years this treatment strategy has been considered by many the most promising tool in order to improve survival of locally advanced tumors of the stomach. Aim of this study is to evaluate the clinical significance and the possible impact on survival of tumor downstaging after neoadjuvant chemotherapy followed by D2-gastrectomy in an accurately staged and thoroughly selected group of 30 locally advanced gastric cancer patients, with a complete follow-up of at least 3 years. In our series, T-downstaging was observed in 43.3% of patients; this parameter, along with other known prognostic factors, was found to be significantly associated with survival (p <0.05). Moreover, T-downstaging induced by preoperative chemotherapy was significantly associated with absence of residual tumor (R0) and no lymph node metastases (ypN0) (p <0.05). At multivariate analysis, R0-resection was the only independent prognostic factor (HR 9.439, p <0.0001). According to our results we feel encouraged to consider neoadjuvant chemotherapy a promising modality for increasing the R0-percentage by tumor downstaging.

Neural anatomy of the transverse carpal ligament.

Carpal tunnel syndrome is one of the most commonly diagnosed disorders of the upper extremity. The etiology of the neuropathy is known to be associated with many disorders, with the etiology of carpal tunnel syndrome mainly attributable to ischemia of the median nerve. The purpose of this study was to determine the presence of neural elements within the transverse carpal ligament. Fourteen transverse carpal ligaments were harvested from seven male and seven female fresh frozen cadavers with an average age of 76 years. The tissues were stained with S-100 using a standard immunoperoxidase technique used to localize neural tissue. The transverse carpal ligament consisted of interwoven bundles of fibrous connective tissue. It was found to have an intraligamentous and extraligamentous neural network consisting mostly of free nerve endings and pacinian corpuscles. Ruffini's corpuscles were not identified. This study showed that there is neural innervation to the transverse carpal ligament. Pacinian corpuscles have been shown to be mechanoreceptors which respond to changes in joint position, whereas free nerve endings have been identified as nociceptors. Neural innervation were present in the transverse carpal ligament, and the nociceptive information relayed by these neural elements may contribute to the pain associated with carpal tunnel syndrome. In addition to being a mechanical wrist stabilizer, the transverse carpal ligament also may play a role in proprioception of the wrist.

Experimental lead arthropathy: an animal model.

BACKGROUND: We previously demonstrated short-term effects of intra-articular lead on joint structures in an animal model. We now present histopathologic findings in animals studied over a more extended period. METHODS: Twelve female New Zealand White rabbits had identical lead or stainless steel pellets, or a sham arthrotomy (without implant) inserted in both front knees. The rabbits were killed 4 at a time at 6, 10, and 14 weeks after implantation, and the knee joint structures were evaluated histologically for changes in the synovium, articular cartilage, and meniscus. RESULTS: Histology of the tibial articular surface, femoral articular surface, medial meniscus, lateral meniscus, and synovium showed greater signs of degeneration in the knees with lead implants than controls at all time periods. CONCLUSION: Intrasynovial lead, which does not undergo fibrous encapsulation, has been linked to lead intoxication. Clinical and experimental reports support removal of lead bodies from articular areas in an attempt reduce or slow the degeneration of affected joints. Nonmechanical effects of lead on intraarticular structures may lead to degenerative changes

Infrared spectroscopy of human tissue. I. Differentiation and maturation of epithelial cells in the human cervix.

Infrared spectral results for the different epithelial layers of human cervical squamous tissue are reported. The layers, representing different cellular maturation stages, exhibit quite different spectral patterns. Thus, infrared spectroscopy presents a powerful tool to monitor cell maturation and differentiation. Furthermore, a detailed understanding of the spectra of the individual layers of tissue permit a proper interpretation of the state of health of cells exfoliated from such tissue. Part II of this series describes the use of the spectral information presented here to interpret the infrared spectra of exfoliated cells.

Infrared spectroscopy of human tissue. II. A comparative study of spectra of biopsies of cervical squamous epithelium and of exfoliated cervical cells.

A comparison of infrared absorption spectra obtained from the different layers of squamous epithelium from the human cervix, and infrared spectra obtained from exfoliated cervical cells, is presented. Infrared spectroscopy has been shown (in part I of this series) to be a sensitive tool to monitor maturation and differentiation of human cervical cells; therefore, this spectroscopic technique provides new insights into the composition and state of health of exfoliated cells.

Histologic comparison of posterior cruciate ligaments from arthritic and age-matched knee specimens.

Twenty-four posterior cruciate ligaments (PCLs) harvested at the time of total knee arthroplasty (TKA) were histologically compared with an age-matched group of 36 PCLs harvested from above-knee amputations, cadavers, and bone bank donors. Ligaments were considered histologically abnormal and degenerative if either loose, mucoid, myxoid, or cystic changes were noted. The magnitude of degeneration was defined as normal, slight, mild, moderate, or marked, based on the amount of tissue demonstrating change. Examination of the PCLs from the TKA group demonstrated 17% normal ligaments, 20% with mild focal changes, and 63% with marked degenerative changes. The control group demonstrated 45% normal cruciate ligaments and 33% with slight, 11% with mild, and 11% with moderate focal changes. No PCL from the control group showed marked changes. The overall degenerative changes between these two groups were found to be statistically significant (P < .001). This study demonstrated that the PCL obtained at the time of TKA is characterized by distinct histologic degenerative changes that are different from age-related changes (P < .001) and that the PCL is not spared degenerative changes in involved osteoarthritic knees. This may help explain the finding that the PCL in osteoarthritic knees is biomechanically abnormal. Many studies have reported excellent results with TKA systems that retain the PCL, implying that a completely normal PCL is not required or that neural input is sufficient for proper kinematic knee function in knees that have undergone total joint arthroplasty.